Activation of YAP attenuates hepatic damage and fibrosis in liver ischemia-reperfusion injury

Liu, Yuan; Lu, Tianhuan; Zhang, Cheng; Xu, Jin; Xue, Zhengze; Busuttil, Ronald W.; Xu, Ning; Xia, Qiang; Kupiec‐Weglinski, Jerzy W.; Ji, Hongxiu

doi:10.1016/j.jhep.2019.05.029

Cited by 174 publications

(145 citation statements)

References 39 publications

Supporting

Mentioning

119

Contrasting

Order By: Relevance

“…Our research combined with previous studies proved that VDR and YAP1 was extremely downregulated in cholestasis (Anakk et al, 2013;Gonzalez-Sanchez et al, 2017) and both VDR −/− mice and YAP1 −/− mice were more sensitive to cholestasis-induced liver injury (Bai et al, 2012;Firrincieli et al, 2013). Two recent studies proved that YAP1 activation could attenuate hepatic damage and fibrosis in liver ischemia-reperfusion injury and inhibit NLRP3 activation (Li et al, 2019;Liu et al, 2019). In our research, VDR agonist Calcipotriol could negatively regulate NLRP3 inflammation activation both in vivo and in vitro.…”

Section: Discussionsupporting

confidence: 72%

“…YAP1 activation was previously recognized as an important role to promote liver regeneration and alleviate liver injury in cholestasis by two studies (Bai et al, 2012;Tharehalli et al, 2018). Besides a resent study has shown that activation of YAP could attenuate hepatic damage and fibrosis in liver ischemiareperfusion injury (Liu et al, 2019). It is highly likely that YAP activation plays an important role in hepatic protection, regeneration, anti-fibrosis in acute liver injury.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Calcipotriol Inhibits NLRP3 Signal Through YAP1 Activation to Alleviate Cholestatic Liver Injury and Fibrosis

Wang

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

Cholestasis is common in multiple clinical circumstances. The NOD-like receptor protein 3 (NLRP3) inflammasome pathway has been demonstrated to play an important role in liver injury and fibrosis induced by cholestasis. We previously proved that MCC950, a selective NLRP3 inhibitor, alleviates liver fibrosis and injury in experimental liver cholestasis induced by bile-duct ligation (BDL) in mice. Herein, we investigate the role of calcipotriol, a potent vitamin D receptor agonist, in experimental liver cholestasis, test its therapeutic efficacy, and explore its potential protective mechanism. C57BL/6 mice were made to undergo BDL or fed the 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet to establish two classic cholestatic models. Calcipotriol was administered intraperitoneally to these mice daily. Serum makers of liver damage and integrity, liver histological changes, levels of liver pro-fibrotic markers, bile acid synthetases and transporters were measured in vivo. The underlying mechanism by which calcipotriol alleviates cholestatic liver injury and fibrosis was further investigated. The results of the current study demonstrated that calcipotriol supplement significantly alleviate cholestatic liver injury and fibrosis. Moreover, calcipotriol supplement markedly inhibited NLRP3 inflammasome pathway activation to alleviate liver injury and fibrosis in vivo and inhibit hepatic stellate cell (HSC) activation in vitro. In addition, VDR agonist calcipotriol exert inhibitory effect on NLRP3 inflammasome activation through activating yes-associated protein 1 (YAP1). In conclusion, our findings proved that calcipotriol suppressed the NLRP3 signal by activating YAP1 to alleviate liver injury and retard fibrogenesis in cholestasis.

show abstract

Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Calcipotriol Inhibits NLRP3 Signal Through YAP1 Activation to Alleviate Cholestatic Liver Injury and Fibrosis

Wang

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Supporting our results, a recent clinical study reported that high YAP expression in LT recipients was associated with better preserved liver function. 28 Here we identified changes in YAP expression before liver graft retrieval from DBD donors, making this signalling pathway a potential novel therapeutic target.…”

Section: Discussionmentioning

confidence: 93%

FGF15 improves outcomes after brain dead donor liver transplantation with steatotic and non-steatotic grafts in rats

Gulfo

Rotondo

León

et al. 2020

Journal of Hepatology

View full text Add to dashboard Cite

“…Loss of phosphorylation, whether by decreased kinase activity or through increased phosphatase activity, is associated with nuclear localization of Yap and the subsequent activation of downstream proliferative and anti-apoptotic gene programs 11,15 . Liu et al 16 showed that activation of Yap attenuates hepatic damage and fibrosis in liver ischemia-reperfusion injury. Deletion of Yap in the liver leads to defects in both hepatocyte survival and biliary epithelial cell development 17 .…”

Section: Introductionmentioning

confidence: 99%

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

et al. 2020

View full text Add to dashboard Cite

Previous studies have shown that tumor necrosis factor (TNF)-α is a mediator of hepatotoxicity in liver injury. Moreover, TNF-α has also been reported to have a protective effect in liver regeneration, yet the function of TNF-α during liver injury remains controversial. Here, we report that the concentration of TNF-α determines its functions. High concentrations of TNF-α could aggravate LPS-induced liver injury. However, the TNF-α level was unchanged during APAP-induced liver injury, which exerted a protective effect. We expected that the concentration of TNF-α may affect its function. To test this hypothesis, TNF-α −/− rats or hepatocyte cells were treated with different concentrations of TNF-α. We found low TNF-α could reduce the levels of ALT and AST in the plasma of TNF-α −/− rats and promote the proliferation of hepatocyte cells. However, the levels of ALT and AST increased gradually with increasing TNF-α concentration after reaching the lowest value. Moreover, we showed that TNF-α affects the cell proliferation and cell death of hepatocytes by regulating Yap activity. Low TNF-α promoted Yap1 nuclear translocation, triggering the proliferation of hepatocytes. However, high TNF-α triggered the phosphorylation and inactivation of Yap1, preventing its nuclear import and consequently promoting cell death. Collectively, our findings provide novel evidence that the concentration of TNF-α is an important factor affecting its function in liver injury, which may provide a reference for the clinical treatment of liver injury.

show abstract

Activation of YAP attenuates hepatic damage and fibrosis in liver ischemia-reperfusion injury

Cited by 174 publications

References 39 publications

Calcipotriol Inhibits NLRP3 Signal Through YAP1 Activation to Alleviate Cholestatic Liver Injury and Fibrosis

Calcipotriol Inhibits NLRP3 Signal Through YAP1 Activation to Alleviate Cholestatic Liver Injury and Fibrosis

FGF15 improves outcomes after brain dead donor liver transplantation with steatotic and non-steatotic grafts in rats

The concentration of tumor necrosis factor-α determines its protective or damaging effect on liver injury by regulating Yap activity

Contact Info

Product

Resources

About