Liver sinusoidal endothelial cells in hepatic fibrosis.

Liver sinusoidal endothelial cells in hepatic fibrosis.
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DOI:
10.1002/hep.27376
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发表时间:
2015-05
期刊:
影响因子:
13.5
通讯作者:
DeLeve, Laurie D.
DeLeve, Laurie D.
中科院分区:
医学1区
文献类型:
--
作者:
DeLeve, Laurie D.

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毛细血管化、肝窦内皮细胞(LSEC)开窗的缺乏和组织化基底膜的形成不仅先于纤维化,而且还允许肝星状细胞活化和纤维化。因此,LSEC表型的失调是纤维化过程中的关键步骤。VEGF刺激的NO非依赖性途径和VEGF刺激的NO依赖性途径都是维持分化的LSEC表型所必需的。NO依赖性途径在毛细作用中受损,并且NO下游的该途径的激活恢复体内LSEC分化。体内LSEC分化的恢复促进HSC静止,增强纤维化的消退,并防止肝硬化的进展。
Capillarization, lack of liver sinusoidal endothelial cell (LSEC) fenestration and formation of an organized basement membrane, not only precedes fibrosis, but is also permissive for hepatic stellate cell activation and fibrosis. Thus dysregulation of the LSEC phenotype is a critical step in the fibrotic process. Both a VEGF-stimulated, NO-independent pathway and a VEGF-stimulated NO-dependent pathway are necessary to maintain the differentiated LSEC phenotype. The NO-dependent pathway is impaired in capillarization and activation of this pathway downstream from NO restores LSEC differentiation in vivo. Restoration of LSEC differentiation in vivo promotes HSC quiescence, enhances regression of fibrosis, and prevents progression of cirrhosis.
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