Legends for Supplemental Data

Transcript

1 Legends for Supplemental Data Supplemental Fig. 1. Top molecular and cellular functions identified by Ingenuity Pathway Analysis after 6 h (left) and 24 h (right) of exposure of mouse pancreatic islets to IL-1β and IFN-γ (p<0.05 by Fischer s exact test). Supplemental Fig. 2. Canonical pathways identified by Ingenuity Pathway Analysis after 6 h (left) and 24 h (right) of exposure of mouse pancreatic islets to IL-1β and IFN-γ (p<0.05 by Fischer s exact test). Supplemental Fig. 3. Top molecular and cellular functions identified by Ingenuity Pathway Analysis after 6 h (left) and 24 h (right) of co-treatment (1,25(OH) 2 D 3 in combination with IL-1β and IFN-γ) as compared to cytokine exposure alone (IL-1β and IFN-γ) of mouse pancreatic islets (p<0.05 by Fischer s exact test). Supplemental Fig. 4. Effect of 1,25(OH) 2 D 3 on qrt-pcr mrna expression of chemokines and cytokines in IL-1β- and IFN-γ-treated human islets. Islets were cultured for 24 h with ) control medium; ) 10-8 M 1,25(OH) 2 D 3 ; ) 50 U/ml IL-1β and 100 U/ml IFN-γ; and ) 10-8 M 1,25(OH) 2 D 3, 50 U/ml IL-1β and 100 U/ml IFN-γ. Data are presented as three individual islet isolations (HI 1, HI 2 and HI 3). Supplemental Table 1. Manual classification of selected genes differentially regulated by IL-1β and IFN-γ vs vehicle in islets after 6 and 24 h of in vitro exposure (n=4 independent experiments expressed as fold change vs respective control. *p<0.05; **p<0.02; ***p<0.01; ****p<0.001 vs vehicle by Welch s t-test. Con: Control. 1,25: 1,25(OH) 2 D 3. Cyt: IL-1β and IFN-γ). Supplemental Table 2. Manual classification of selected genes differentially regulated by cotreatment (1,25(OH) 2 D 3 in combination with IL-1β and IFN-γ) as compared to cytokine exposure alone (IL-1β and IFN-γ) in pancreatic islets (n=4 independent experiments expressed as fold change vs respective control. *p<0.05; **p<0.02; ***p<0.01; ****p<0.001 Welch s t-test. Con: Control. 1,25: 1,25(OH) 2 D 3. Cyt: IL-1β and IFN-γ).

2 1 Supplemental materials and methods Chemotaxis assay C57BL/6 islets were cultured in BioWhittaker UltraCULTURE Serum-Free Medium (Lonza, Basel, Switzerland) supplemented with Glutamax -I (Life Technologies, Carlsbad, CA) and 5 µg/ml geneticin. Exposure to 1,25(OH) 2 D 3 and cytokines was similar to that described in section 2.2. except for a prolonged culture period of 3 days. For the chemotaxis assay thioglycolate-elicited peritoneal cells from 8-12 week old C57BL/6 mice were seeded in the top chamber of Costar transwell plates ( cells per well) (5.0 µm, Corning Inc., Corning, NY), while conditioned islet medium was added to the lower chambers of the transwell plate. Positive and negative controls consisted of UltraCULTURE Serum-Free medium with or without recombinant murine MIP-1α (50ng/ml, PeproTech), respectively. Following an incubation time of 2 h at 37 C in 5% CO 2, the cells in the lower chamber were harvested and stained for monocyte specific cell surface markers. To minimize nonspecific binding, the cells were first pre-incubated with anti-cd16/cd32 (clone 2.4G2). Cells were then labeled with directly conjugated mabs: CD45, CD11b, Ly6C, F4/80 (San Diego, CA, USA). Dead cells were excluded by using the Fixable Live/Dead Yellow stain according to the manufacturer s specifications (Invitrogen, Carlsbad, CA). The absolute number of migrated monocytes was determined by CountBright absolute counting beads (Invitrogen). Data acquisition was performed on a Gallios TM flow cytometer (Beckman Coulter, Brea, CA, USA) and KaluzaTM software was used for data analysis. Monocytes were determined as Ly6C + CD11b + F4/80 - within the viable leukocyte (CD45 + ) gate Assessment of NF-κB activity Islets were cultured for 24 h in the presence of 1,25(OH) 2 D 3 or vehicle, after which they were stimulated for 30 min with IL-1β and IFN-γ at 37 C. Thereafter, islets were washed twice in ice-cold PBS supplemented with 1:100 Phosphatase Inhibitor Cocktail 2 (Sigma-Aldrich, St. Louis, MO) and lysed in Complete lysis buffer (Active Motif, Carlsbad, CA). Protein concentrations were determined

3 28 29 by the Coomassie method. Binding activity of NF-κB p52 subunits was determined by the TransAM NF-κB assay according to the manufacturer s instructions (Active Motif).

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8 6 h 24 h Cyt Cyt Accession Symbol Gene name / functional group vs Con vs Con Arginine metabolism, Nitric oxide formation NM_ Arg1 arginase, liver **** **** NM_ Nos2 (inos) nitric oxide synthase 2, inducible **** **** Glucose metabolism, Krebs cycle NM_ Aco1 aconitase **** **** NM_ Aco2 aconitase 2, mitochondrial **** *** NM_ Aldh2 aldehyde dehydrogenase 2, mitochondrial *** *** NM_ Cs citrate synthase * NM_ Eno1 enolase 1, alpha non-neuron **** 1.38 *** NM_ Fh1 fumarate hydratase **** **** NM_ Gck glucokinase *** NM_ Glud1 glutamate dehydrogenase **** 1.01 NM_ Gpam glycerol-3-phosphate acyltransferase, mitochondrial *** 1.06 NM_ Gpd1 glycerol-3-phosphate dehydrogenase 1 (soluble) **** 1.07 NM_ Gpi1 glucose phosphate isomerase ** 1.3 ** NM_ Hk2 hexokinase **** 2.78 *** NM_ Idh1 isocitrate dehydrogenase 1 (NADP+), soluble **** **** NM_ Idh2 isocitrate dehydrogenase 2 (NADP+), mitochondrial **** 1.45 *** NM_ Idh3b isocitrate dehydrogenase 3 (NAD+), beta **** 1.14 ** NM_ Idh3g isocitrate dehydrogenase 3 (NAD+), gamma * **** NM_ Ldha lactate dehydrogenase A ** NM_ Ldhd lactate dehydrogenase D 1.38 *** NM_ Mdh1 malate dehydrogenase 1, NAD (soluble) **** -1.4 **** NM_ Mdh2 malate dehydrogenase 2, NAD (mitochondrial) * ** NM_ Ogdh oxoglutarate dehydrogenase (lipoamide) *** **** NM_ P4hb prolyl 4-hydroxylase, beta polypeptide **** * NM_ Pcx pyruvate carboxylase *** *** NM_ Pdha1 pyruvate dehydrogenase E1 alpha *** **** NM_ Pdhb pyruvate dehydrogenase (lipoamide) beta **** NM_ Pdk1 pyruvate dehydrogenase kinase, isoenzyme *** NM_ Pdk2 pyruvate dehydrogenase kinase, isoenzyme **** *** NM_ Pdk3 pyruvate dehydrogenase kinase, isoenzyme *** 1.54 ** NM_ Pdk4 pyruvate dehydrogenase kinase, isoenzyme **** **** NM_ Pfkfb2 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase *** *** NM_ Pfkfb3 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (glycolytic 9.8 **** 4.08 **** activator) NM_ Pfkl phosphofructokinase, liver, B-type **** 1.46 * NM_ Pfkm phosphofructokinase, muscle **** -2 **** NM_ Pfkp phosphofructokinase, platelet 6 **** 2.67 *** NM_ Pgam5 phosphoglycerate mutase family member *** 1.54 *** NM_ Pklr pyruvate kinase liver and red blood cell *** *** NM_ Pkm2 pyruvate kinase, muscle *** 1.03 NM_ Sdhb succinate dehydrogenase complex, subunit B, iron sulfur (Ip) * 1.06 NM_ Slc2a1 solute carrier family 2 (facilitated glucose transporter), member *** 4.92 *** NM_ Slc2a2 (Glut-2) solute carrier family 2 (facilitated glucose transporter), member **** **** NM_ Suclg1 succinate-coa ligase, GDP-forming, alpha subunit NM_ Tpi1 triosephosphate isomerase **** 1.38 ** Lipid metabolism NM_ Acaca acetyl-coenzyme A carboxylase alpha *** **** NM_ Acat1 acetyl-coenzyme A acetyltransferase **** **** NM_ Acly ATP citrate lyase **** **** NM_ Acsl1 acyl-coa synthetase long-chain family member *** NM_ Acsl3 acyl-coa synthetase long-chain family member *** 1.3 **** NM_ Acsl5 acyl-coa synthetase long-chain family member **** 1.52 **** NM_ Ckb creatine kinase, brain * **** NM_ Ckmt1 creatine kinase, mitochondrial 1, ubiquitous -1.2 * 1.74 * NM_ Cpt1a carnitine palmitoyltransferase 1a, liver 1.14 ** 2.14 **** NM_ Cpt2 carnitine palmitoyltransferase NM_ Dagla diacylglycerol lipase, alpha **** -1.7 * NM_ Dgkg diacylglycerol kinase, gamma 7.43 **** 2.08 *

9 NM_ Elovl2 elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, *** **** yeast)-like 2 NM_ Elovl6 ELOVL family member 6, elongation of long chain fatty acids 1.18 ** ** (yeast) NM_ Fads1 fatty acid desaturase **** **** NM_ Fads2 fatty acid desaturase **** * NM_ Fasn fatty acid synthase **** **** NM_ Gyk glycerol kinase ** **** NM_ Lipc lipase, hepatic 1.51 **** 1.65 **** NM_ Lpl lipoprotein lipase *** ** NM_ Srebf2 sterol regulatory element binding factor * * NM_ Vldlr very low density lipoprotein receptor Interferon-γ signaling NM_ Ifnar2 interferon (alpha and beta) receptor **** 2.52 **** NM_ Ifngr1 interferon gamma receptor NM_ Ifngr2 interferon gamma receptor **** 3.03 **** NM_ Irf1 interferon regulatory factor **** 9.97 **** NM_ Irf1 interferon regulatory factor **** 1.64 **** NM_ Irf2 interferon regulatory factor **** 1.47 **** NM_ Irf3 interferon regulatory factor NM_ Irf7 interferon regulatory factor **** **** NM_ Irf8 interferon regulatory factor **** 2.29 **** NM_ Irf9 interferon regulatory factor **** 5.79 **** NM_ Jak1 Janus kinase **** 1.49 **** NM_ Jak2 Janus kinase **** 2.02 *** NM_ Jak3 Janus kinase **** 1.52 *** NM_ Socs1 suppressor of cytokine signaling **** 1.48 **** NM_ Socs2 suppressor of cytokine signaling U72673 Socs3 suppressor of cytokine signaling * 1.04 NM_ Socs3 suppressor of cytokine signaling **** 1.41 ** NM_ Socs6 suppressor of cytokine signaling * 1.47 * NM_ Socs7 suppressor of cytokine signaling *** NM_ Stat1 signal transducer and activator of transcription **** **** NM_ Stat2 signal transducer and activator of transcription **** 7.85 **** NM_ Stat3 signal transducer and activator of transcription **** 2.1 *** NM_ Stat5b signal transducer and activator of transcription 5B ** NM_ Stat6 signal transducer and activator of transcription **** 1.63 *** NF-κB regulation NM_ Ikbke inhibitor of kappab kinase epsilon 9.22 **** 2.99 **** NM_ Ikbkg inhibitor of kappab kinase gamma 1.38 *** 2.14 **** NM_ Irak2 interleukin-1 receptor-associated kinase **** 2.43 **** NM_ Irak3 interleukin-1 receptor-associated kinase **** 1.92 **** NM_ Nfkb1 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1, 3.36 **** 1.29 ** p105 NM_ Nfkb2 nuclear factor of kappa light polypeptide gene enhancer in B-cells 2, **** 3.86 **** p49/p100 NM_ Nfkbia nuclear factor of kappa light polypeptide gene enhancer in B-cells 10.2 **** 5.43 **** inhibitor, alpha NM_ Nfkbib nuclear factor of kappa light polypeptide gene enhancer in B-cells 2.7 **** 1.95 **** inhibitor, beta NM_ Nfkbie nuclear factor of kappa light polypeptide gene enhancer in B-cells 3.26 **** 1.49 * inhibitor, epsilon NM_ Nfkbiz nuclear factor of kappa light polypeptide gene enhancer in B-cells 4.61 **** 2.69 **** inhibitor, zeta NM_ Tank TRAF family member-associated Nf-kappa B activator 1.91 **** 1.13 ** NM_ Tbk1 TANK-binding kinase **** 1.64 *** NM_ Tifa TRAF-interacting protein with forkhead-associated domain **** 7.59 **** NM_ Tnfaip3 (A20) tumor necrosis factor, alpha-induced protein **** 3.32 **** NM_ Tnip1 TNFAIP3 interacting protein 1 (obs candidate gene in psoriarisis) 6.72 **** 4.97 **** NM_ Tnip2 TNFAIP3 interacting protein *** 1.5 **** NM_ Traf2 TNF receptor-associated factor **** 1.66 ** Other transcription factors NM_ Batf2 basic leucine zipper transcription factor, ATF-like **** 3.39 **** NM_ Bcl10 B-cell leukemia/lymphoma *** 1.32 ***

10 NM_ Bcl3 B-cell leukemia/lymphoma **** 3.96 **** NM_ Bcl6 B-cell leukemia/lymphoma **** 4.2 *** NM_ Bcor BCL6 interacting corepressor *** NM_ Bmp2 bone morphogenetic protein **** NM_ Cebpb CCAAT/enhancer binding protein (C/EBP), beta 2.79 **** 1.88 **** NM_ Cebpd CCAAT/enhancer binding protein (C/EBP), delta **** 5 **** NM_ Cebpg CCAAT/enhancer binding protein (C/EBP), gamma 1.62 **** 1.63 *** NM_ Dll1 delta-like 1 (Drosophila) 3.99 **** 1.98 *** NM_ Fos FBJ osteosarcoma oncogene NM_ Foxo1 forkhead box O1-1.6 **** **** NM_ Foxo4 forkhead box O **** **** NM_ Hes6 hairy and enhancer of split 6 (Drosophila) **** *** NM_ Hif1a hypoxia inducible factor 1, alpha subunit 2.27 **** 1.24 * NM_ Ifitm1 interferon induced transmembrane protein **** 1.48 **** NM_ Isl1 ISL1 transcription factor, LIM/homeodomain **** **** NM_ Jag2 jagged *** **** NM_ Jun (c-jun) Jun oncogene 5.86 **** 4.13 *** NM_ Junb Jun-B oncogene 2.72 **** 1.9 *** NM_ Jund Jun proto-oncogene related gene d 1.53 *** 1.4 *** NM_ Klf5 Kruppel-like factor **** 1.51 *** NM_ Klf6 Kruppel-like factor **** 2.62 *** NM_ Neurod1 neurogenic differentiation *** NM_ Neurog3 neurogenin **** *** NM_ Nkx2-2 NK2 transcription factor related, locus 2 (Drosophila) **** **** NM_ Nkx6-1 NK6 homeobox **** -1.8 *** NM_ Pax6 paired box gene **** **** NM_ Pdx1 pancreatic and duodenal homeobox **** **** NM_ Ppard peroxisome proliferator activator receptor delta 1.55 **** 1.12 NM_ Sec16a SEC16 homolog A (S. cerevisiae) *** NM_ Srebf1 sterol regulatory element binding transcription factor *** **** NM_ Tcf7l2 transcription factor 7-like 2, T-cell specific, HMG-box 1.31 *** **** NM_ Tnfaip2 tumor necrosis factor, alpha-induced protein **** 5.76 **** NM_ Trib2 tribbles homolog 2 (Drosophila) **** **** NM_ Wif1 Wnt inhibitory factor **** 1.74 *** NM_ Xbp1 X-box binding protein *** *** Splicing machinery, chromatin regulation NM_ Hdac2 histone deacetylase *** NM_ Hdac3 histone deacetylase **** *** NM_ Hdac5 histone deacetylase **** *** NM_ Hdac9 histone deacetylase **** *** NM_ Pcgf2 polycomb group ring finger *** 1.06 BC Pcgf5 polycomb group ring finger *** NM_ Sfrs1 splicing factor, arginine/serine-rich 1 (ASF/SF2) **** NM_ Sfrs17b splicing factor, arginine/serine-rich 17b *** NM_ Sfrs18 splicing factor, arginine/serine-rich *** *** NM_ Sfrs18 splicing factor, arginine/serine-rich **** NM_ Sfrs2 splicing factor, arginine/serine-rich 2 (SC-35) *** NM_ Sfrs2ip splicing factor, arginine/serine-rich 2, interacting protein -1.2 * 1.3 * NM_ Sfrs3 splicing factor, arginine/serine-rich 3 (SRp20) ** NM_ Sfrs4 splicing factor, arginine/serine-rich 4 (SRp75) 1.47 **** 1.48 * NM_ Sfrs6 splicing factor, arginine/serine-rich **** NM_ Sfrs7 splicing factor, arginine/serine-rich * ** Chemokines, cytokines, adhesion molecules NM_ Ccl11 (Eotaxin) chemokine (C-C motif) ligand **** 1.77 NM_ Ccl2 (MCP-1) chemokine (C-C motif) ligand **** **** NM_ Ccl20 chemokine (C-C motif) ligand **** 1.22 * NM_ Ccl28 chemokine (C-C motif) ligand **** 1.23 ** NM_ Ccl5 (RANTES) chemokine (C-C motif) ligand **** 4.21 **** NM_ Ccl7 (MCP-3) chemokine (C-C motif) ligand *** 2.73 *** NM_ Ccl8 (MCP-2) chemokine (C-C motif) ligand **** 3 **** NM_ Ccrl2 chemokine (C-C motif) receptor-like **** 4.92 **** NM_ Csf1 colony stimulating factor 1 (macrophage) 5.13 **** 3.43 *** NM_ Cx3cl1 (fractalkine) chemokine (C-X3-C motif) ligand **** ****

11 NM_ Cxcl1 (Gro-α) chemokine (C-X-C motif) ligand **** 4.06 **** NM_ Cxcl10 (IP-10) chemokine (C-X-C motif) ligand **** **** NM_ Cxcl11 (Itac) chemokine (C-X-C motif) ligand **** **** NM_ Cxcl16 chemokine (C-X-C motif) ligand **** 8.57 **** NM_ Cxcl2 (Gro-beta) chemokine (C-X-C motif) ligand **** 2.78 * NM_ Cxcl5 (ENA-78) chemokine (C-X-C motif) ligand **** **** NM_ Cxcl9 (Mig) chemokine (C-X-C motif) ligand **** **** NM_ Icam1 intercellular adhesion molecule **** **** NM_ Il10rb interleukin 10 receptor, beta 1.84 **** 1.45 **** NM_ Il13ra1 interleukin 13 receptor, alpha **** 3.1 **** NM_ Il15 interleukin **** 1.64 ** NM_ Il15ra interleukin 15 receptor, alpha chain 2 **** 1.66 *** NM_ Il17c interleukin 17C 2.1 *** NM_ Il17rc interleukin 17 receptor C 1.34 *** 1.44 **** NM_ Il17rd interleukin 17 receptor D 1.29 *** 1.28 NM_ Il17re interleukin 17 receptor E -1.5 **** **** NM_ Il18 interleukin **** NM_ Il18bp interleukin 18 binding protein 7.71 **** 9.58 **** NM_ Il18r1 interleukin 18 receptor **** 3.51 **** NM_ Il1a interleukin 1 alpha *** NM_ Il1b interleukin 1 beta 1.74 *** 1.89 **** NM_ Il1r2 interleukin 1 receptor, type II 1.59 *** 1.28 *** NM_ Il1rap interleukin 1 receptor accessory protein 1.82 **** 1.23 *** NM_ Il1rn interleukin 1 receptor antagonist 1.48 *** 1.76 **** NM_ Il20rb interleukin 20 receptor beta 1.49 *** 1 NM_ Il21 interleukin *** 1.28 ** NM_ Il27 interleukin *** 1.22 NM_ Il28b interleukin 28B 1.79 *** 1.5 *** NM_ Il33 interleukin **** 1.28 NM_ Il34 interleukin *** 1.27 ** NM_ Il4ra interleukin 4 receptor, alpha 2 **** 1.65 *** NM_ Il6 interleukin **** **** NM_ Il6ra interleukin 6 receptor, alpha **** **** NM_ Il7 interleukin **** 1.64 **** NM_ Tnf tumor necrosis factor 3.9 **** 1.28 NM_ Vcam1 vascular cell adhesion molecule **** 2.14 **** Other innate immune response components NM_ Cfb complement factor B 59.1 **** **** NM_ Ddx58 (RIG-I) DEAD (Asp-Glu-Ala-Asp) box polypeptide **** 4.34 **** NM_ Ddx60 DEAD (Asp-Glu-Ala-Asp) box polypeptide **** 6.45 **** NM_ Defb1 defensin beta **** 3.06 *** NM_ Hamp hepcidin antimicrobial peptide **** **** NM_ Ido1 indoleamine 2,3-dioxygenase **** 5.74 **** NM_ Ido2 indoleamine 2,3-dioxygenase *** NM_ Ifih1 (MDA5) interferon induced with helicase C domain **** 1.76 **** NM_ Irg1 immunoresponsive gene **** 8.46 **** NM_ Mx1 myxovirus (influenza virus) resistance **** 4.21 **** NM_ Oas1a 2'-5' oligoadenylate synthetase 1A 9.6 **** 4.98 **** NR_ Oas1b 2'-5' oligoadenylate synthetase 1B 7.12 **** 3.92 *** NM_ Oas1c 2'-5' oligoadenylate synthetase 1C 1.43 *** * NM_ Oas2 2'-5' oligoadenylate synthetase **** 11.9 **** NM_ Oas3 2'-5' oligoadenylate synthetase **** 1.52 ** NM_ Oasl1 2'-5' oligoadenylate synthetase-like **** 1.99 **** NM_ Oasl2 2'-5' oligoadenylate synthetase-like **** **** NM_ Tirap toll-interleukin 1 receptor (TIR) domain-containing adaptor protein 1.54 *** 1.03 NM_ Tlr2 toll-like receptor **** 3.05 **** NM_ Tlr3 toll-like receptor **** 1.62 **** Proteasome, antigen presentation NM_ Cd74 CD74 antigen (invariant polypeptide of major histocompatibility **** **** complex, class II antigen-associated) NM_ H2-Ea histocompatibility 2, class II antigen E alpha NM_ H2-M3 histocompatibility 2, M region locus **** 1.62 **** NM_ H2-T23 histocompatibility 2, T region locus **** 6.39 **** NM_ Prr3 proline-rich polypeptide

12 NM_ Psmb8 proteasome (prosome, macropain) subunit, beta type 8 (large 14.3 **** **** multifunctional peptidase 7) NM_ Psme2 proteasome (prosome, macropain) 28 subunit, beta 5.16 **** 5.77 **** NM_ Ring1 ring finger protein *** * NM_ Slc39a7 solute carrier family 39 (zinc transporter), member **** NM_ Tap1 (Mtp-1) transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) **** **** NM_ Tap2 (Mtp-2) transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) 8.41 **** 6.9 **** NM_ Vps52 vacuolar protein sorting 52 (yeast) * (there are also a large number of up-regulated HLA-related molecules) Hormones, growth factors NM_ Adm adrenomedullin ** NM_ Chga chromogranin A *** NM_ Chgb chromogranin B 1.17 * 1.17 NM_ Fgf1 fibroblast growth factor **** ** NM_ Furin furin (paired basic amino acid cleaving enzyme) NM_ Gcg glucagon NM_ Iapp islet amyloid polypeptide NM_ Igf2bp2 insulin-like growth factor 2 mrna binding protein **** 3.34 *** NM_ Ins1 insulin I *** NM_ Ins2 insulin II NM_ Pcsk1 (Pc1) proprotein convertase subtilisin/kexin type * **** NM_ Pcsk2 (Pc2) proprotein convertase subtilisin/kexin type *** **** NM_ Pdgfb platelet derived growth factor, B polypeptide 1.61 *** 1.52 NM_ Sst somatostatin -1.5 **** * NM_ Tgfb1 transforming growth factor, beta ** 1.6 ** NM_ Vegfa vascular endothelial growth factor A **** 1.16 *** NM_ Vegfb vascular endothelial growth factor B *** Hormone and growth factor receptors NM_ Galr1 galanin receptor **** **** NM_ Gcgr glucagon receptor **** ** NM_ Ghr growth hormone receptor **** **** NM_ Gipr gastric inhibitory polypeptide receptor **** *** NM_ Glp1r glucagon-like peptide 1 receptor **** **** NM_ Igf1r insulin-like growth factor I receptor 2.04 **** 1.6 * NM_ Igf2r insulin-like growth factor 2 receptor 1.48 **** 1.06 NM_ Insr insulin receptor -1.4 **** 1.08 NM_ Insr insulin receptor **** 1.02 NM_ Oxtr oxytocin receptor **** **** NM_ Pdgfrb platelet derived growth factor receptor, beta polypeptide *** NM_ Prlhr prolactin releasing hormone receptor **** * BC Prlr prolactin receptor -2.6 **** **** NM_ Prlr prolactin receptor **** *** NM_ Tgfbr1 transforming growth factor, beta receptor I *** NM_ Vdr vitamin D receptor *** *** Free radical scavenger, DNA damage response NM_ Cat catalase 1.23 * 2.88 **** NM_ Ccnd1 cyclin D **** **** NM_ Ccnh cyclin H **** *** NM_ Cdk5 cyclin-dependent kinase **** *** NM_ Cdkl1 cyclin-dependent kinase-like 1 (CDC2-related kinase) **** ** NM_ Cnnm2 cyclin M *** NM_ Gadd45b growth arrest and DNA-damage-inducible 45 beta 6.57 **** **** NM_ Gadd45g growth arrest and DNA-damage-inducible 45 gamma 1.72 *** 1.85 **** NM_ Gpx1 glutathione peroxidase **** 2.63 **** NM_ Gpx2 glutathione peroxidase **** 1.06 NM_ Gsr glutathione reductase 1.95 **** 1.69 **** NM_ Gsta3 glutathione S-transferase, alpha **** NM_ Gstm7 glutathione S-transferase, mu *** *** NM_ Gsto1 glutathione S-transferase omega ** 2.55 *** NM_ Hmox1 heme oxygenase (decycling) **** 7 **** NM_ Mt1 metallothionein **** 4.55 **** NM_ Mt2 metallothionein **** 8.89 **** NM_ Parp12 poly (ADP-ribose) polymerase family, member **** 4.93 **** NM_ Parp2 poly (ADP-ribose) polymerase family, member *** -1.01

13 NM_ Parp3 poly (ADP-ribose) polymerase family, member **** 1.82 **** NM_ Parp9 poly (ADP-ribose) polymerase family, member **** 6.35 **** NM_ Pdrg1 p53 and DNA damage regulated * 1.2 NM_ Sod2 (MnSOD) superoxide dismutase 2, mitochondrial 4.47 **** 2.65 **** NM_ Txn1 thioredoxin *** NM_ Txnrd1 thioredoxin reductase **** 1.41 *** Cell cycle NM_ Ccnd1 cyclin D **** **** NM_ Ccnh cyclin H **** *** NM_ Cdk11b cyclin-dependent kinase 11B **** NM_ Cdk5 cyclin-dependent kinase **** *** NM_ Cnnm2 cyclin M **** **** NM_ Cnnm2 cyclin M *** Endoplasmic reticulum stress, translational regulation NM_ Atf3 activating transcription factor **** 6.89 **** NM_ Atf4 activating transcription factor ** 1.01 NR_ Atp2a2 (Serca2b) ATPase, Ca++ transporting, cardiac muscle, slow twitch **** *** NM_ Calb1 calbindin **** **** NM_ Ddit3 (Chop) DNA-damage inducible transcript *** 9.11 **** NM_ Derl1 Der1-like domain family, member * 1.51 *** NM_ Edem1 ER degradation enhancer, mannosidase alpha-like * 1.53 *** NM_ Eef1a2 eukaryotic translation elongation factor 1 alpha *** *** NM_ Eif1a eukaryotic translation initiation factor 1A 1.86 **** 1.04 * NM_ Eif2a eukaryotic translation initiation factor 2a NM_ Eif2ak2 eukaryotic translation initiation factor 2-alpha kinase **** 1.56 **** NM_ Eif2ak3 (Perk) eukaryotic translation initiation factor 2 alpha kinase *** 1.52 * NM_ Eif2c1 eukaryotic translation initiation factor 2C, **** *** NM_ Eif2c3 eukaryotic translation initiation factor 2C, **** 1.06 NM_ Eif2c4 eukaryotic translation initiation factor 2C, *** NM_ Eif4e1b eukaryotic translation initiation factor 4E family member 1B *** -1.1 NM_ Eif4ebp1 eukaryotic translation initiation factor 4E binding protein **** 1.35 * NM_ Eif5b eukaryotic translation initiation factor 5B 1.43 **** 1.56 **** NM_ Eif6 eukaryotic translation initiation factor **** 1.98 **** NM_ Ern1 (IRE1) endoplasmic reticulum (ER) to nucleus signalling *** 1.27 * AK Hspa1b (Hsp70) heat shock protein 1B NM_ Hspa5 (Bip) heat shock protein **** NM_ Hspa8 heat shock protein *** 1.43 **** NM_ Hspa9 heat shock protein **** NM_ Hspbap1 Hspb associated protein *** 1.38 **** NM_ Hspd1 heat shock protein 1 (chaperonin) *** 1.24 *** NM_ Hsph1 heat shock 105kDa/110kDa protein * 1.45 * NM_ Hyou1 (Orp150) hypoxia up-regulated **** **** NM_ Man2a1 mannosidase 2, alpha *** **** NM_ Mars methionine-trna synthetase * NM_ Psen1 presenilin **** 1.3 **** NM_ Sec61a1 Sec61 alpha 1 subunit (S. cerevisiae) -1.1 *** **** NM_ Sec61a2 Sec61, alpha subunit 2 (S. cerevisiae) **** Apoptosis related NM_ Aen apoptosis enhancing nuclease 1.58 **** 2.42 **** NM_ Apaf1 apoptotic peptidase activating factor **** 1.86 **** NM_ Bag1 BCL2-associated athanogene 1 (oncogene; increases Bcl2 act.) 1.4 **** 1.68 **** NM_ Bag2 BCL2-associated athanogene ** *** NM_ Bag3 BCL2-associated athanogene **** 1.27 NM_ Bak1 BCL2-antagonist/killer **** 1.61 **** NM_ Bax BCL2-associated X protein **** NM_ Bbc3 (Puma) BCL2 binding component * NM_ Bcl2l1 (Bcl-XL) BCL2-like **** 2.1 **** NM_ Bid BH3 interacting domain death agonist 3.73 **** 2.47 **** NM_ Bik BCL2-interacting killer 1.37 *** NM_ Casp1 caspase **** 6.54 **** NM_ Casp12 caspase *** 2.24 *** NM_ Casp2 caspase **** 1.31 ** NM_ Casp3 caspase **** 2.55 **** NM_ Casp4 caspase 4, apoptosis-related cysteine peptidase **** 8.34 ****

14 NM_ Casp7 caspase **** 5.27 **** NM_ Casp8 caspase **** 1.11 * NM_ Cflar CASP8 and FADD-like apoptosis regulator 1.57 **** *** NM_ Dap death-associated protein 1.39 *** 1.42 **** NM_ Dapl1 death associated protein-like **** **** NM_ Daxx (Fas Fas death domain-associated protein 2.64 **** 1.27 *** associated) NM_ Fas Fas (TNF receptor superfamily member 6) **** **** NM_ Hrk (Dp5) harakiri, BCL2 interacting protein (contains only BH3 domain) NM_ Moap1 modulator of apoptosis 1 (obs interacts with Bax) 1.6 **** 1.06 * NM_ Pdcd6ip programmed cell death 6 interacting protein (obs apoptosis 1.32 **** 1.61 **** NM_ Ppp1r15a protein phosphatase 1, regulatory (inhibitor) subunit 15A 1.34 *** 3.64 **** NM_ Tmbim1 transmembrane BAX inhibitor motif containing *** 1.68 **** NM_ Trib3 tribbles homolog 3 (Drosophila) 1.7 ** 4.67 **** ENSMUST Kinases, phosphatases Alpk1 alpha-kinase **** 2.46 **** Alpk1 alpha-kinase **** 2.39 **** Alpk1 alpha-kinase **** 2.14 *** NM_ Dusp1 dual specificity phosphatase 1 (obs dusps phosphatases modulate 2.18 ** 2.26 * ERK/MAPKs) NM_ Dusp10 dual specificity phosphatase **** 1.54 NM_ Dusp16 dual specificity phosphatase **** 2.53 ** NM_ Dusp18 dual specificity phosphatase **** **** NM_ Dusp19 dual specificity phosphatase **** *** NM_ Dusp3 dual specificity phosphatase 3 (vaccinia virus phosphatase VH **** 1.08 related) NM_ Dusp6 dual specificity phosphatase *** NM_ Dusp8 dual specificity phosphatase **** 3.55 ** NM_ Madd MAP-kinase activating death domain **** *** NM_ Mapk6 mitogen-activated protein kinase **** 1.66 * NM_ Mapkapk2 MAP kinase-activated protein kinase **** 2.27 **** NM_ Pak1 p21 protein (Cdc42/Rac)-activated kinase **** 1.82 **** NM_ Prkcd protein kinase C, delta 1.47 *** 1.49 **** NM_ Ptpn1 protein tyrosine phosphatase, non-receptor type **** 1.56 **** NM_ Ptpn23 protein tyrosine phosphatase, non-receptor type *** 1.61 *** Others NM_ Adcy6 adenylate cyclase **** *** NM_ Alox12 arachidonate 12-lipoxygenase 5.02 **** 2.56 **** NM_ Capn1 calpain **** 1.32 **** NM_ Gad1 (Gad67) glutamic acid decarboxylase **** * NM_ Iigp1 interferon inducible GTPase **** **** NM_ Pld1 phospholipase D **** 1.62 *** NM_ Ubd ubiquitin D **** **** NM_ Ubtd1 ubiquitin domain containing *** 1.19 ** NM_ Ucp2 uncoupling protein 2 (mitochondrial, proton carrier) *** ****

15 6 h (fold change) 24 h (fold change) Cyt 1.25+Cyt 1.25 Cyt 1.25+Cyt 1.25 Accession Symbol Gene name / functional group vs Con vs Cyt vs Con vs Con vs Cyt vs Con Cell cycle and cell growth NM_ Ccnc cyclin C * -1,15 * ** 1.3 *** NM_ Ccnh cyclin H **** ,1 ** *** 1.45 *** 1,23 * NM_ Cdk1 cyclin-dependent kinase **** *** NM_ Fmnl2 formin-like **** 1.15 ** 2,16 **** 1.51 *** 1.54 *** 2,06 **** NM_ Mlst8 MTOR associated protein, LST8 homolog (S. cerevisiae) * **** 1.48 *** 1.01 Cell death NM_ Dapl1 death associated protein-like **** ,71 *** **** *** NM_ Ggct gamma-glutamyl cyclotransferase 2.25 **** -1.4 *** ** Cellular stress, DNA damage NM_ Cat catalase 1.23 * 1.36 *** 1,57 *** 2.88 **** 1.95 *** 1,79 *** NM_ Gadd45g growth arrest and DNA-damage-inducible 45 gamma 1.72 *** ,13 *** 1.85 **** *** 1.06 NM_ Hmox1 heme oxygenase (decycling) **** 1.41 ** **** NM_ Nqo1 NAD(P)H dehydrogenase, quinone **** *** -1,16 * NF-κB signaling NM_ Ikbke (IKKε) inhibitor of kappab kinase epsilon 9.22 **** **** *** 1.05 NM_ Nfkb2 (p52) nuclear factor of kappa light polypeptide gene enhancer in B-cells 2, p49/p **** **** **** NM_ Nfkbib nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta 2.7 **** **** *** -1 (IκBβ) NM_ Nfkbie nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon 3.26 **** **** * *** (IκBε) NM_ Relt RELT tumor necrosis factor receptor **** 1.42 *** 1,7 **** **** 1.33 ** 1,6 **** NM_ Tnfaip8 tumor necrosis factor, alpha-induced protein **** ** 1.37 **** NM_ Tnfrsf11b tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) 6.81 **** 1.8 ** *** 2.37 **** NM_ Tnfrsf9 tumor necrosis factor receptor superfamily, member **** **** -1.6 ** -1.1 NM_ Trib3 tribbles homolog 3 (Drosophila) 1.7 ** **** 1.39 *** 1.09 Chemokines and cytokines NM_ Ccl2 chemokine (C-C motif) ligand **** *** **** ** (MCP-1) NM_ Ccl5 chemokine (C-C motif) ligand **** *** 1,13 * 4.21 **** (RANTES) NM_ Ccl8 chemokine (C-C motif) ligand **** * **** *** 1.04 (MCP-2) NM_ Cxcl1 chemokine (C-X-C motif) ligand **** -1.4 *** **** *** 1 NM_ Cxcl11 chemokine (C-X-C motif) ligand **** -1.4 *** **** -3 **** 1.05

16 NM_ Cxcl16 chemokine (C-X-C motif) ligand **** -1.3 *** **** -1.4 * -1 NM_ Cxcl2 chemokine (C-X-C motif) ligand **** -1.9 *** * NM_ Cxcl9 chemokine (C-X-C motif) ligand **** **** * 1 NM_ Il15 interleukin **** *** -1,1 *** 1.64 ** * 1.01 NM_ Il18 interleukin **** *** NM_ Il18r1 interleukin 18 receptor **** 1.9 **** **** 2.1 * 1.05 NM_ Il1rl2 interleukin 1 receptor-like *** *** 1.16 NM_ Il4i1 interleukin 4 induced **** -1.4 **** **** **** -1,17 ** NM_ Il6 interleukin **** * **** NM_ Il7 interleukin **** 1.46 *** **** 2.09 **** 1.06 Other immune response components NM_ Bat5 HLA-B associated transcript **** *** ** 1.04 NM_ C1s complement component 1, s subcomponent **** ** **** NM_ C3 complement component **** 2.29 **** **** 3.27 *** 1.08 NM_ Ceacam1 carcinoembryonic antigen-related cell adhesion molecule **** 1.54 ** 2,43 *** 2.98 **** ,55 *** NM_ Chi3l1 chitinase 3-like **** 2.36 **** **** 5.12 **** 1.07 (Ykl-40) NM_ Colec12 collectin sub-family member * 1.09 * ** **** 1.17 NM_ Defb1 defensin beta **** ,41 ** 3.06 *** 1.26 * 1.26 NM_ Hamp hepcidin antimicrobial peptide **** **** * -1.1 NM_ Icam1 intercellular adhesion molecule **** * **** -1.3 * NM_ Ifi204 interferon activated gene **** **** ** (Ifi16) NM_ Iigp1 interferon inducible GTPase **** **** 1.34 *** 1.02 NM_ Irg1 immunoresponsive gene **** 1.27 *** **** ,15 *** NM_ Irgm1 immunity-related GTPase family M member **** **** 1.44 ** NM_ Ltf lactotransferrin 8.3 **** 1.54 ** **** 1.51 *** NM_ Mx1 myxovirus (influenza virus) resistance **** **** 1,18 * 4.21 **** ,21 ** NR_ Mx2 myxovirus (influenza virus) resistance **** **** *** 1.1 NM_ Oas2 2'-5' oligoadenylate synthetase **** **** * NM_ Oasl1 2'-5' oligoadenylate synthetase-like **** **** *** 1.03 NM_ Orm1 orosomucoid ** 2.1 *** 1.03 NM_ Samhd1 SAM domain and HD domain, **** 1.63 **** **** 1.34 *** 1,08 * NM_ Tlr2 toll-like receptor **** **** 1.53 **** NM_ Tlr3 toll-like receptor **** ,1 ** 1.62 **** 1.32 * NM_ Tnfaip2 tumor necrosis factor, alpha-induced protein **** *** **** * NM_ Vcam1 vascular cell adhesion molecule **** **** **** 1.04 Ceramide, sphingomyelin, ganglioside NM_ A4galt alpha 1,4-galactosyltransferase 1.57 *** 1.33 *** 1,19 * 1.94 *** NM_ Smpdl3b sphingomyelin phosphodiesterase, acid-like 3B 2.25 **** *** ** NM_ St3gal5 ST3 beta-galactoside alpha-2,3-sialyltransferase **** 1.49 *** 2,33 **** **** 1.77 *** 1,73 ***

17 NM_ St8sia1 ST8 alpha-n-acetyl-neuraminide alpha-2,8-sialyltransferase **** 1.57 **** 1,54 **** **** 1.87 **** 1.52 Cell-to-cell contact, extracellular matrix NM_ Adam8 a disintegrin and metallopeptidase domain *** ,06 * 1.78 *** ** -1 NM_ Adamts4 a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, *** *** -1.5 *** NM_ Adamts6 a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, **** ** NM_ Amigo2 adhesion molecule with Ig like domain **** 2,69 **** 2.15 *** 3.09 **** 2,41 **** NM_ Frem2 Fras1 related extracellular matrix protein **** 1.61 **** ** ,25 * NM_ Itga6 integrin alpha **** 1.36 *** NM_ Lpp LIM domain containing preferred translocation partner in lipoma 1.53 *** *** **** 1.08 NM_ Mmp13 matrix metallopeptidase **** 4.01 **** 1,58 * 5.92 **** 3.95 **** 3,45 *** NM_ Mpp7 membrane protein, palmitoylated 7 (MAGUK p55 subfamily member 7) ** 2.37 **** 2,15 **** **** 2.81 **** 1,78 **** NM_ Nedd9 neural precursor cell expressed, developmentally down-regulated gene **** 1,95 **** 1.86 **** 2.41 **** 1,59 *** NM_ Pcdhb20 protocadherin beta * **** 1.51 *** NM_ Plau plasminogen activator, urokinase *** ** 1.07 NM_ Tgfbi transforming growth factor, beta induced 1.27 ** **** *** Exocytosis, intracellular trafficking, cytoskeleton NM_ Arhgap26 Rho GTPase activating protein **** **** **** 1.04 NM_ Arl6 ADP-ribosylation factor-like *** **** 1.32 *** NM_ Bet1 blocked early in transport 1 homolog (S. cerevisiae) **** * -1,11 * -3.9 **** 1.51 *** 1 NM_ Capg capping protein (actin filament), gelsolin-like *** **** 1.04 NM_ Clasp1 CLIP associating protein * **** 1.74 **** NM_ Golga1 golgi autoantigen, golgin subfamily a, **** *** 1.45 *** 1.08 NM_ Golim4 golgi integral membrane protein **** ,14 ** *** 1.33 ** NM_ Gsn gelsolin *** *** *** NM_ Mal2 mal, T-cell differentiation protein **** *** 1.34 ** -1,15 * NM_ Mylip myosin regulatory light chain interacting protein 1.48 *** **** -1,17 ** 1.62 **** *** NM_ Pls1 plastin 1 (I-isoform) **** ,1 *** **** 1.33 *** 1.06 NM_ Pstpip2 proline-serine-threonine phosphatase-interacting protein ** ** * NM_ Rab3b RAB3B, member RAS oncogene family *** *** NM_ Rab9b RAB9B, member RAS oncogene family **** 1.42 **** 1,8 **** **** 1.44 *** 1.2 NM_ Rnd3 Rho family GTPase **** *** -1,18 *** 4.42 *** NM_ Snx14 sorting nexin **** ,13 *** *** 1.34 ** NM_ Snx33 sorting nexin *** 1.31 *** 1,18 ** NM_ Snx7 sorting nexin *** *** * ** BC Stx11 syntaxin **** **** **** -1.3 *** NM_ Stx7 syntaxin **** 1.34 **** *** 1.31 **** 1.15 NM_ Stxbp6 syntaxin binding protein 6 (amisyn) **** -1.4 *** -1,31 *** **** ,2 *** NM_ Synj2 synaptojanin *** 1.83 **** 2,05 **** * 1.77 *** 1,84 **** NM_ Tmem27 transmembrane protein **** 1.23 **** 1,13 *** **** 1.69 **** 1,35 **** NM_ Trak2 trafficking protein, kinesin binding ** ,46 *** *** 1.39 *** 1,34 ****

18 Hormone and growth factor signaling NM_ Egfr epidermal growth factor receptor 1.64 **** 1.82 **** 1,15 *** 2.48 **** NM_ Ereg epiregulin 2.33 **** **** *** NM_ Fgf7 fibroblast growth factor * **** *** -1,25 * NM_ Irs2 insulin receptor substrate *** *** *** 1.08 NM_ Kit kit oncogene -1.4 * ,31 * 1.53 *** ** NM_ Pappa2 pappalysin *** *** *** NM_ Pappa2 pappalysin **** ,28 *** *** ** NM_ Pdgfa platelet derived growth factor, alpha **** 1.48 **** 1,52 **** 1.26 * 1.3 ** 1,46 **** NM_ Pdgfb platelet derived growth factor, B polypeptide 1.61 *** 1.53 **** NM_ Ralgds ral guanine nucleotide dissociation stimulator 3.2 **** 1.33 *** 1,52 *** 1.41 ** ,2 **** NM_ Vipr2 (VPAC2) vasoactive intestinal peptide receptor ,96 *** 1.92 **** 1.48 **** 1,51 * Transcription factors etc. NM_ Ankrd52 ankyrin repeat domain * *** 1.33 *** 1.13 NM_ Anks4b ankyrin repeat and sterile alpha motif domain containing 4B * *** 1.35 *** NM_ Bhlha15 basic helix-loop-helix family, member a * **** 1.46 *** 1.15 NM_ Dll1 delta-like 1 (Drosophila) 3.99 **** ** *** * -1,14 * NM_ Hes1 hairy and enhancer of split 1 (Drosophila) *** ,19 * 1.6 ** ** NM_ Id2 inhibitor of DNA binding **** *** -1,26 *** 2.01 *** NM_ Isl1 ISL1 transcription factor, LIM/homeodomain **** **** 1.3 * NM_ Lifr leukemia inhibitory factor receptor ** 1.26 * 1,35 * **** 1.39 *** 1,19 * NM_ Lmo1 LIM domain only *** *** *** 1.06 NM_ Myc myelocytomatosis oncogene 1.54 *** *** -1,33 * 4.74 *** NM_ Neurod1 neurogenic differentiation *** *** 1.43 *** 1,09 *** NM_ Nr1d1 nuclear receptor subfamily 1, group D, member **** ** NM_ Nrip1 nuclear receptor interacting protein * 1.36 ** 1,2 **** 1.88 *** 1.31 ** 1,35 *** NM_ Pax6 paired box gene **** **** 1.31 *** NM_ Snai2 snail homolog 2 (Drosophila) ,66 *** 1.81 ** 1.52 **** 1,4 * NM_ Tceal1 transcription elongation factor A (SII)-like **** ,21 * **** 1.34 ** NM_ Twist2 twist homolog 2 (Drosophila) 1.24 * *** ** 1,07 * Glucose metabolism NM_ Agl amylo-1,6-glucosidase, 4-alpha-glucanotransferase **** 1.17 **** 1,07 *** **** 1.48 *** 1.09 NM_ G6pc2 glucose-6-phosphatase, catalytic, **** 1.22 **** **** 1.54 **** 1,12 * NM_ Gck glucokinase ** *** 1.32 *** 1.07 NM_ Idh1 isocitrate dehydrogenase 1 (NADP+), soluble **** 1.37 **** 1,26 * **** 1.78 *** 1.05 NM_ Ldha lactate dehydrogenase A ** ** 1.09 NM_ Nubpl nucleotide binding protein-like ,15 *** ** 1.43 ** 1.02 NM_ Nudt14 nudix (nucleoside diphosphate linked moiety X)-type motif **** **** 1.3 *** 1.08 NM_ Pdha1 pyruvate dehydrogenase E1 alpha *** 1.3 *** **** 1.83 **** 1,25 ***

19 NM_ Pfkfb3 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase **** -1.5 **** **** NM_ Pgm5 phosphoglucomutase *** 2.01 ** 1,94 **** Lipid and cholesterol metabolism NM_ Abca1 ATP-binding cassette, sub-family A (ABC1), member **** ** -1,31 **** 1.53 **** *** NM_ Abcg1 ATP-binding cassette, sub-family G (WHITE), member *** ** -1,29 **** 2.8 **** **** NM_ Acsl4 acyl-coa synthetase long-chain family member **** 1.16 * *** 1.47 **** NM_ Cyp24a1 cytochrome P450, family 24, subfamily a, polypeptide **** 56.2 **** 98,19 **** **** 88,95 **** NM_ Dgat1 diacylglycerol O-acyltransferase * **** 1.32 *** 1 NM_ Dgat2 diacylglycerol O-acyltransferase **** 1,34 **** 3.48 **** 3.1 **** 1,58 * NM_ Dhcr24 24-dehydrocholesterol reductase **** 1.19 ** **** 1.34 *** NM_ Dhrs9 dehydrogenase/reductase (SDR family) member **** 1.4 **** 1,56 **** NM_ Far1 fatty acyl CoA reductase *** **** 1.37 *** 1,2 *** NM_ Nceh1 arylacetamide deacetylase-like ** **** 1.49 **** 1,29 *** NM_ Naaa N-acylethanolamine acid amidase 1.13 *** 1.7 **** *** 1.66 **** 1.01 NM_ Pex7 peroxisomal biogenesis factor *** **** 1.37 ** 1.02 NM_ Pla2g7 phospholipase A2, group VII (platelet-activating factor acetylhydrolase, plasma) *** *** 1,8 *** NM_ Rdh9 retinol dehydrogenase *** ** ** Metabolism of amino acids and nucleic acids NM_ Bphl biphenyl hydrolase-like (serine hydrolase, breast epithelial mucin-associated antigen) **** ,7 **** ** 1.64 *** 1,55 **** NM_ Cpn1 carboxypeptidase N, polypeptide *** **** 1.46 **** 1.06 NM_ Entpd3 ectonucleoside triphosphate diphosphohydrolase *** 1.31 *** 1,34 *** 1.42 *** 1.41 *** 1,37 *** NM_ Suox sulfite oxidase *** **** 1.53 ** 1.07 NM_ Upp1 uridine phosphorylase **** **** ** Inositol phosphate metabolism NM_ Impa1 inositol (myo)-1(or 4)-monophosphatase ** 1,36 **** ** 1.67 *** 1,38 **** NM_ Inppl1 inositol polyphosphate phosphatase-like **** 1.81 **** 1,54 **** *** 1.26 *** 1,24 *** Metabolism of drugs etc. NM_ Adh1 alcohol dehydrogenase 1 (class I) -3.9 **** 1.8 **** 1,74 **** **** 2.83 **** 1,57 ** NM_ Aldh5a1 aldhehyde dehydrogenase family 5, subfamily A *** 1.31 *** NM_ Car13 carbonic anhydrase **** **** *** 1.19 NM_ Car8 carbonic anhydrase *** ** -1,31 * ** *** NM_ Sult1c2 sulfotransferase family, cytosolic, 1C, member **** 2.06 **** 2,28 **** **** 1,9 *** NM_ Ugt2b34 UDP glucuronosyltransferase 2 family, polypeptide B *** **** 1.9 **** 1.07 Splicing machinery, RNA modification NR_ Adarb1 adenosine deaminase, RNA-specific, B **** 1.44 *** 1,15 ** *** 1.67 **** 1.19 NM_ Cstf3 cleavage stimulation factor, 3' pre-rna, subunit * **** 1.33 *** 1,23 * NM_ Hdac6 histone deacetylase **** 1.34 **** **** 1.68 *** -1,1 ** NM_ Ints7 integrator complex subunit **** *** 1.31 *** -1 NM_ Nap1l2 nucleosome assembly protein 1-like **** 1.31 *** -1,26 *** NM_ Prpf4b PRP4 pre-mrna processing factor 4 homolog B (yeast) *** 1.37 *** 1,34 *** **** 1,29 ***

20 NM_ Trrap transformation/transcription domain-associated protein * **** 1.35 *** -1 Transport and homeostasis of ions etc. NM_ Abca8b ATP-binding cassette, sub-family A (ABC1), member 8b 2.06 **** ,05 ** 1.95 **** 1.38 ** NM_ Abcc2 ATP-binding cassette, sub-family C (CFTR/MRP), member ** **** 1.4 *** 1.11 NM_ Best3 bestrophin **** 1.24 **** 1,12 *** *** 1.42 * 1,44 **** NM_ Kcnh6 potassium voltage-gated channel, subfamily H (eag-related), member **** 1.32 *** 1,64 **** **** 1.66 *** 1,49 **** NM_ Mmgt2 membrane magnesium transporter * 1.46 **** 1,6 **** *** 1.74 *** 1,51 *** NM_ P2rx4 purinergic receptor P2X, ligand-gated ion channel **** 1.32 **** 1,91 **** *** 1.64 ** 1,54 **** NM_ Scn9a sodium channel, voltage-gated, type IX, alpha **** *** *** 1.4 ** NM_ Scn9a sodium channel, voltage-gated, type IX, alpha **** ** **** NM_ Scnn1g sodium channel, nonvoltage-gated 1 gamma 2.57 *** **** ,22 * NM_ Sgk1 serum/glucocorticoid regulated kinase **** ,41 **** ** *** NM_ Slc16a12 solute carrier family 16 (monocarboxylic acid transporters), member **** 1.6 *** **** 1.8 **** 1.05 NM_ Slc22a23 solute carrier family 22, member **** 1.51 **** **** 1.07 NM_ Slc25a35 solute carrier family 25, member **** 1.63 **** NM_ Slc31a2 solute carrier family 31, member **** ,8 *** ** 1.41 *** 1,56 **** NM_ Slc33a1 solute carrier family 33 (acetyl-coa transporter), member **** * -1,08 * **** 1.35 *** 1.03 NM_ Slc35a5 solute carrier family 35, member A * *** 1.32 ** NM_ Slc35d3 solute carrier family 35, member D **** * **** 1.33 **** 1.1 NM_ Slc35f2 solute carrier family 35, member F **** 2.82 **** 1,25 *** 1.51 **** NM_ Slc8a1 solute carrier family 8 (sodium/calcium exchanger), member **** **** 1.35 ** 1.07 NM_ Slco1a6 solute carrier organic anion transporter family, member 1a *** 1.56 **** 1,47 **** *** 2.18 *** 1,72 **** NM_ Stc1 stanniocalcin ** 1.54 ** **** ,03 * NM_ Steap1 six transmembrane epithelial antigen of the prostate **** 1-1,41 *** 2.61 **** 1.41 ** 1.04 NM_ Steap4 STEAP family member **** **** 2.02 *** Intracellular signaling NM_ Akap6 A kinase (PRKA) anchor protein *** *** -1,33 *** NM_ Arrb2 arrestin, beta **** 1.35 *** 1,76 **** *** 1.63 *** 1,86 *** NM_ Asb4 ankyrin repeat and SOCS box-containing **** *** **** **** NM_ Cnksr1 connector enhancer of kinase suppressor of Ras **** * **** *** 1.07 NM_ Dock8 dedicator of cytokinesis **** 1.15 * 1,14 * **** 1.77 *** 1.12 NM_ Ffar1 free fatty acid receptor **** **** -1,3 ** **** NM_ Gna14 guanine nucleotide binding protein, alpha **** 1.24 ** 1,6 *** 2.56 **** 1.38 ** 1.55 NM_ Grk5 G protein-coupled receptor kinase **** 1.45 *** 1,29 *** *** 1.66 **** 1,29 * NM_ Grtp1 GH regulated TBC protein **** **** -1,25 **** **** NM_ Mras muscle and microspikes RAS 1.25 * *** 1.4 *** NM_ Pde3b phosphodiesterase 3B, cgmp-inhibited **** ,46 *** *** 1.44 **** 1,21 **** NM_ Plcxd2 phosphatidylinositol-specific phospholipase C, X domain containing *** **** *** 1,21 *** NM_ Rasd2 RASD family, member *** **** 1.39 ** -1 NM_ Sdc1 syndecan **** 1.76 **** *** NM_ Sdc4 syndecan **** *** **** **** -1,18 *