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The current study aimed to investigate the biological function of irisin on hepatic fibrosis. A mouse model of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)-induced hepatic fibrosis was established. CCl<jats:sub>4<\/jats:sub>-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 CCl<jats:sub>4<\/jats:sub>-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.<\/jats:p>","DOI":"10.1515\/hsz-2020-0251","type":"journal-article","created":{"date-parts":[[2021,1,23]],"date-time":"2021-01-23T01:56:40Z","timestamp":1611367000000},"page":"703-715","source":"Crossref","is-referenced-by-count":20,"title":["Irisin ameliorates endoplasmic reticulum stress and liver fibrosis through inhibiting PERK-mediated destabilization of HNRNPA1 in hepatic stellate cells"],"prefix":"10.1515","volume":"402","author":[{"given":"Xin","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Pathophysiology , Guizhou Medical University , No. 9 Beijing Road , Yunyan District , Guiyang City 550004 , Guizhou Province , China"},{"name":"Department of Imaging , Affiliated Hospital of Guizhou Medical University , Guiyang City 550004 , Guizhou Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery , Affiliated Hospital of Guizhou Medical University , Guiyang City 550004 , Guizhou Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine , Guizhou Provincial People\u2019s Hospital , Guiyang City 550002 , Guizhou Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Tian","sequence":"additional","affiliation":[{"name":"Central Laboratory, Guiyang Maternal and Child Health Hospital , Guiyang City 550004 , Guizhou Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Guiyang Maternal and Child Health Hospital , Guiyang City 550004 , Guizhou Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6763-3492","authenticated-orcid":false,"given":"Qin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology , Guizhou Medical University , No. 9 Beijing Road , Yunyan District , Guiyang City 550004 , Guizhou Province , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"2023040406521015001_j_hsz-2020-0251_ref_001_w2aab3b7b7b1b6b1ab2b1b1Aa","doi-asserted-by":"crossref","unstructured":"Ahmad, A. and Ahmad, R. 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