Hippo通路因子Yap调控鼠肝星状细胞活化过程

• the mechanical properties of the extracellular matrix have profound effects on YAP activity and HSC activation in vitro
Fig. 6. Culture on soft substrates inhibits YAP signalling.
Fig. 2. IHC of YAP in non-fibrotic and fibrotic mouse and human liver.
• livers from hepatitis C patients showed strong nuclear staining in perisinusoidal cells in the liver lobules and also in myofibroblastic cells located in the fibrotic areas
Fig. 1. Identification of YAP target genes in in vitro and in vivo activated mHSCs.
wk.baidu.com
Fig. 2. IHC of YAP in non-fibrotic and fibrotic mouse and human liver. • fibrous livers had elevated levels of nuclear and cytoplasmic YAP in biliary cells and hepatocytes
• total levels of YAP and those of its phosphorylated form were robustly elevated 10 h after seeding, while the levels of Yap mRNA were only slightly increased • activation of YAP is a fast and very early event during HSC activation.
Fig. 7. In vivo inhibition of YAP signaling with verteporfin.
Fig. 7. In vivo inhibition of YAP signaling with verteporfin.
the commonly assayed YAP target genes Ankrd1 and Ctgf showed a striking upregulation
Fig. 1. Identification of YAP target genes in in vitro and in vivo activated mHSCs.
• inhibited YAP activity by treating cells with verteporfin (VP)维替泊芬, a pharmacological inhibitor of YAP that disruptsthe YAP/TEAD complex
• VP abolished the induction of Acta2 and Col1a1 expression that is normally observed after seven days and suppressed the induction of Ankrd1 and Ctgf expression and the changes in cell morphology normally observed after 10 h • VP treatment did not affect cell viability Fig. 5. Inhibition of YAP blocks HSC activation in vitro.
Fig. 3. YAP protein expression and subcellular localization.
• • 10 h after in vitro activation by plating, more than 70% of cells had nuclear YAP, and 100% of cells had nuclear YAP after ten days. When HSCs were activated in vivo, about 50% of HSCs had nuclear YAP
• HSCs with knockdown of YAP did not induce these genes（Acta2, Col1a1, Ankrd1 and Ctgf） Fig. 4. Culture of HSCs in 3D-spheroids reduces YAP signalling and HSCactivation.
汇报人：张兴 导师：刘昌 教授
该 团 队 论 文 发 表 概 况
in vivo：isolated HSCs from healthy mice and on HSCs isolated from mice treated for two or four weeks with CCl4 in vitro：day ten in vitro activated HSCs
Fig. 3. YAP protein expression and subcellular localization.
• culturing HSCs in 3D-spheroids such that they could not attach to any substrate can keep them quiescent. Fig. 4. Culture of HSCs in 3D-spheroids reduces YAP signalling and HSCactivation.