Hepatology:肝纤维化机制的新研究!

2018-02-09 MedSci MedSci原创

肝窦内皮细胞(LSECs)通过血管分泌因子严格调节肝脏动态平衡和疾病的发生。Notch在内皮细胞(EC)中发挥关键作用。目前的研究表明,Notch信号通过Notch胞内结构域(NIC)的诱导EC特异性表达而被激活。近期,一项发表在杂志hepatology上的研究发现,内皮Notch的激活损害了肝脏的平衡。 Notch活化导致穿透的减少和基底膜的增加,并且基因表达谱伴随着LSEC相关基因的减少和EC

肝窦内皮细胞(LSECs)通过血管分泌因子严格调节肝脏动态平衡和疾病的发生。Notch在内皮细胞(EC)中发挥关键作用。目前的研究表明,Notch信号通过Notch胞内结构域(NIC)的诱导EC特异性表达而被激活。

近期,一项发表在杂志hepatology上的研究发现,内皮Notch的激活损害了肝脏的平衡。 Notch活化导致穿透的减少和基底膜的增加,并且基因表达谱伴随着LSEC相关基因的减少和EC连续相关基因的增加,这表明了LSEC去分化。

与此相一致的是,内皮Notch激活增强了由CCl4诱导的肝纤维化。 Notch的激活减弱了eNOS-sGC信号传导,通过YC-1激活sGC可逆转去分化表型。

此外,Notch激活通过下调包括Wnt2a、Wnt9b和HGF的关键肝细胞有丝分裂原破坏LSEC的肝细胞支持血管分泌谱。这导致在静止和再生条件下肝细胞增殖的受损。虽然Wnt2a和Wnt9b的表达依赖于eNOS-sGC信号传导,但是sGC激活剂不能拯救HGF的表达,这提示LSECs是维持肝细胞动态平衡的异质机制。

此项研究结果表明:内皮Notch活化通过eNOS-sGC信号传导导致LSEC去分化和加速肝纤维化,并改变LSECs的血管分泌谱以缓解肝细胞增殖和肝再生。

原始出处:
Duan JL, Ruan B, et al. Endothelial Notch activation reshapes the angiocrine of sinusoidal endothelia to aggravate liver fibrosis and blunt regeneration. Hepatology. 2018 Feb 8. doi: 10.1002/hep.29834.

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    2018-05-06 七师兄

    谢谢分享

    0

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    2018-02-15 大爰

    学习了谢谢分享!!

    0

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    2018-02-11 gwc384
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    2018-02-11 爱吃鱼的菜

    学习了.谢谢!

    0

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    2018-02-10 半夏微凉

    学习了谢谢分享

    0

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