ISSN 1007-7626 CN 11-3870 / Q http / / cjbmb bjmu edu cn Chinese Journal of Biochemistry and Molecular Biology 2012 7 28 7 609 ~ 616 1 2 2 2 * 1 100022 2 102206 liver sinusoidal endothelial cell LSEC Q2 R5 Physiological Function and Pathological Mechanisms of Liver Sinusoidal Endothelial Cell 1 LAO Yuan-Xiang 2 HE Fu-Chu 2 JIANG Ying 2 * 1 College of Life Science and Bio-engineering Beijing University of Technology Beijing 100022 China 2 State Key Laboratory of Proteomics Beijing Proteome Research Center Beijing Institution of Radiation Medicine Beijing 102206 China Abstract Liver sinusoidal endothelial cell LSEC is a main population of liver non-parenchymal cells LSEC has a number of important functions such as filtration phagocytosis antigen presentation immune tolerance When liver is invaded by a variety of pathogens LSECs lose fenestrations and form an underlying basement membrane which are the characteristics of continuous endothelial cells this process was called capillarization LSEC capillarization is a complex life activity induced by several factors and exists in the early stage of diverse liver diseases thus attracted much attention on such a study Herein the research progress in the studies on the physiological function of LSEC and the molecular mechanisms of sinusoidal endothelial cell pathology were introduced in detail First the function of LSEC was summarized Second in addition to studies on the mechanisms of sinusoidal capillarization the roles of sinusoidal capillarization in the mechanisms of diverse liver diseases were also showed Finally It would hopeful that this review can help to promote the studies on sinusoidal endothelial cells Key words liver sinusoidal endothelial cell sinusoidal capillarization pathogenesis 2012-02-20 2012-03-29 No 81170399 * Tel 010-80705299 E-mail jiangying304@ hotmail com Received February 20 2012 Accepted March 29 2012 Supported by National Natural Science Foundation of China No 81170399 * Corresponding author Tel 010-80705299 E-mail jiangying304@ hotmail com
610 28 liver sinusoidal endothelial cell LSEC Tazaki 4SH3 Cas CasΔSH3 LSEC NP31 CasΔSH3-1 platelet LSEC endothelial cell adhesion molecule PECAM / CD31 May 5 1 1 vascular endothelial growth factor VEGF LSEC svegf-r1 VEGF LSEC LSEC 1 VEGF LSEC LSEC LSEC CD31 1 VEGF LSEC LSEC 1 2 LSEC LSEC Kuppfer LSEC 1 LSEC LSEC LSEC 1 LSEC 1 LSEC LSEC 4 1 6 LSEC α- / 2 CD206 α- 3 hepatic I 7 - stellate cell HSC 4 8 1 1 LSEC LSEC LSEC Ganesan 9 - LSEC LSEC LSEC Disse Space LSEC Mousavi 10 LSEC RT-PCR Western LSEC FcγRs FcγIIb2 CD32b SE - 1 IgG IgG Fc FcγRs 2-3 1 3 LSEC LSEC p130cas Crk LSEC
7 611 2 Deleve 11 LSEC 2 1 LSEC LSEC NO LSEC LSEC HSC LSEC VEGF VEGF NO 16 LSEC LSEC LSEC Xie 12 LSEC TAA BAY 60 - Kuppfer 2770 soluble guanylate cyclase sgc Kuppfer LSEC 17 1 4 LSEC 1 endothelin ET-1 hypoxia-inducible factor 1α HIF-1α mrna LSEC LSEC -1 NADPH HIF-1α hepatocyte growth factor HGF -1 ET-BR Kuppfer Wang 13 THP-1 human acute monocytic LSEC HGF leukemia cell line HIF-1α HGF ET-1 ET-BR -1α LSEC regulated upon activation normal T-cell expressed and secreted RANTES / CCL5 chemokine LSEC LSEC CCL5 HGF Yeligar 19 LSEC Ding 14 mrna LSEC p38 MAPK HGF Wnt2-1α JNK-2 JNK-1 2 - DNA 1 vascular endothelial growth factor receptor2 - inhibitor of DNA-binding1 VEGFR2 - Id1 hormone response element VEGFR2 - Id1 HRE-1 HRE-2 AP-1 Fig 1 Kawasaki 15 LSEC TMNK - 1 LSEC -1α / CCL5 - DNA 1α AP-1 Yeligar 18 EMSA -1α HRE
612 28 2 2 26 LSEC LSEC NO enos Straub 27 ~ 29 NOS enos 1 179-1 NADPH 20 ~ LSEC 22 p47 Rac1 NADPH ROS Xie S1P 1 Ptx 23 LSEC G S1P 1 LSEC Gi / o NADPH LSEC Rac1 Gi / o NADPH ROS LSEC Fig 2 NO NO VEGF-A CLEVER-1 common lymphatic endothelial and vascular endothelial receptor-1 BAY 60-2770 Shetty 30 LSEC BAY 60-2770 CLEVER-1 BAY 60-2770 CLEVER-1 T LSEC CLEVER-1 40% T enos ICAM-1 VAP-1 80% T NO NO Lavina 24 CLEVER-1 VAP-1 T adenoviruses containing extracellular superoxide dismutase AdECSOD O 2- cgmp AdECSOD ROS LSEC TEC O 2- LSEC 38 2 3 / Western tumor endothelial cell TEC Jia 31 EHD3 EH-domain containing 3 3 galectin-3 Western hepatocellular carcinoma HCC EHD3 3 2 2 4 25
7 613 Fig 1 Requirement for VEGFR2-Id1 pathway in LSEC-mediated liver regeneration Id1-activated LSECs through laboration of Wnt2 and HGF induce proliferation of juxtaposed hepatocytes 13 Fig 2 Hypothetical scheme of arsenic-stimulated sinusoidal capillarization Arsenic activated NADPH oxidase to induce sinusoidal capillarization by stimulating S1P 1 activation 27-29 University of ROS NO Wisconsin 8 h LSEC LSEC LSEC LSEC 34 LSEC TNFα LSEC TNFα 32 ~ 34 LSEC fibrinogen-like 2 FGL2 LSEC FcγRIIB 35 Seizner 36 FGL2 ROS fgl2 - / - IL-1 IL-6 TNF-α FcγRIIB LSEC
614 28 LSEC FGL2 FcγRIIB LSEC CD31 LSEC SV40 Stolz 37 UW T 18 h LSEC Ac-LDL 48 h LSEC CD31 vwf Kim 42 VEGF VEGFR2 3D LSEC LSEC LSEC - Disse Space 12 d 2 5 SE-1 LSEC 12 d LSEC LSEC LSEC LSEC 38 4 LSEC LSEC LSEC LSEC von Willebrand factor 1 intercellular adhesion molecule 1 ICAM-1 39 LSEC LSEC 40 References 38 1 Couvelard A Scoazec J Y Dauge M C et al Structural and functional differentiation of sinusoidal endothelial cells during liver organogenesis in humans J Blood 1996 87 11 4568-4580 3 2007 35 Pt3 437-439 LSEC 52 3 1089-1099 LSEC LSEC Huebert 41 LSEC 2 Warren A Bertolino P Cogger V C et al Hepatic pseudocapillarization in aged mice J Exp Gerontol 2005 40 10 807-812 3 Botham K M Wheeler-Jones C P Introduction to the Biochemical Society Focused Meeting on Diet and Cardiovascular Health chylomicron remnants and their emerging roles in vascular dysfunction in atherosclerosis J Biochem Soc Trans 4 Tazaki T Sasaki T Uto K et al p130cas Crk-associated substrate plays essential roles in liver development by regulating sinusoidal endothelial cell fenestration J Hepatology 2010 5 May D Djonov V Zamir G et al A transgenic model for conditional induction and rescue of portal hypertension reveals a
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