Sinusoidal endothelial cells prevent rat stellate cell activation and promote reversion to quiescence.
Sinusoidal endothelial cells prevent rat stellate cell activation and promote reversion to quiescence.
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DOI：
10.1002/hep.22351
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发表时间：
2008-09
期刊：
影响因子：
13.5
通讯作者：
Guo, Yumei
中科院分区：
文献类型：
--
作者：
DeLeve, Laurie D.;Wang, Xiangdong;Guo, Yumei
毛细血管化先于肝纤维化。我们假设肝窦内皮细胞（SEC）的毛细血管化允许肝星状细胞（HSC）活化，因此允许纤维化。我们研究了新鲜分离的SEC是否能阻止HSC的活化并促进恢复静止，以及这种作用是否在毛细作用中丧失。将HSC单独培养或与分化或毛细血管化的SEC共培养。结果如下：与新鲜分离的SEC共培养3天后显着降低HSC活化，但与毛细血管化SEC共培养没有影响。抑制一氧化氮（NO）的合成废除SEC抑制HSC活化。当与SEC加血管内皮生长因子（VEGF）（即与维持分化的SEC）共培养时，活化的HSC恢复到静止状态，但与毛细血管化SEC共培养则不然。在SEC加VEGF存在下，激活的HSC向静止的逆转通过抑制NO合成而被废除。为了确定是否确实存在逆转，在将新鲜分离的SEC加VEGF添加到活化的HSC之前和之后3天对活化的和静止的HSC进行计数，并定量静止的HSC中的增殖;化学计量证明逆转。结论：分化的SEC通过VEGF刺激NO的产生，阻止HSC的活化，并促进活化的HSC恢复到静止状态。毛细血管化的SEC不促进HSC静止，因为VEGF刺激的NO产生的损失。
Capillarization precedes hepatic fibrosis. We hypothesize that capillarization of sinusoidal endothelial cells (SEC) is permissive for hepatic stellate cell (HSC) activation and therefore permissive for fibrosis. We examined whether freshly isolated SECs prevent activation of HSCs and promote reversion to quiescence, and whether this effect was lost in capillarization. HSCs were cultured alone or co-cultured with differentiated or capillarized SECs. Results: Co-culture with freshly isolated SECs markedly decreased HSC activation after 3 days in culture, but co-culture with capillarized SEC had no effect. Inhibition of nitric oxide (NO) synthesis abolished SEC suppression of HSC activation. Activated HSCs reverted to quiescence when co-cultured with SEC plus vascular endothelial growth factor (VEGF) (that is, with SECs that maintained differentiation), but co-culture with capillarized SECs did not. Reversion of activated HSCs to quiescence in the presence of SECs plus VEGF was abolished by inhibition of NO synthesis. To establish whether there was indeed reversion, activated and quiescent HSCs were counted before and 3 days after adding freshly isolated SECs plus VEGF to activated HSCs, and proliferation was quantified in quiescent HSCs; the stoichiometry demonstrated reversion. Conclusion: Differentiated SECs prevent HSC activation and promote reversion of activated HSCs to quiescence through VEGF-stimulated NO production. Capillarized SECs do not promote HSC quiescence, because of loss of VEGF-stimulated NO production.
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影响因子：
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