Abstract
Liver fibrosis is a common consequence of chronic liver diseases involved with the activation of hepatic stellate cells (HSCs) and endoplasmic reticulum (ER) stress. Irisin is a small polypeptide hormone that shows beneficial effects on metabolic disorders. The current study aimed to investigate the biological function of irisin on hepatic fibrosis. A mouse model of carbon tetrachloride (CCl4)-induced hepatic fibrosis was established. CCl4-treated mice showed elevated serum levels of AST and ALT, increased collagen accumulation, induced ER stress, and upregulated expressions of pro-fibrotic proteins in the liver compared to the controls. The administration of irisin, however, ameliorated CCl4-induced hepatic fibrosis in both cultured HSCs and mice. PKR-like ER kinase (PERK) is a key component of the ER stress-associated signaling pathway. We found that irisin treatment improved the stability of heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) via regulating the phosphorylation of PERK in mouse livers and isolated HSCs. Also, the knockdown of HNRNPA1 eliminated the hepatoprotective effects of irisin on hepatic fibrosis and ER stress. In summary, this study showed that irisin alleviated ER stress and hepatic fibrosis by inhibiting PERK-mediated HNRNPA1 destabilization, suggesting that irisin may represent a promising therapeutic strategy for patients with liver fibrosis.
Funding source: National Natural Science Foundation of Guizhou Medical University: application of exosome circrna as a biomarker in liver fibrosis and its mechanism
Award Identifier / Grant number: (Grant No. 19nsp021)
Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was supported by Science and Technology Fund Project of Guizhou Health and Family Planning Commission (Grant No. gzwjkj-2018-1-035 and gzwjkj-2018-1-075).
Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
Availability of data and materials: All data generated or analyzed during this study are included in the published article.
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2020-0251).
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