{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:01:30Z","timestamp":1789758090398,"version":"4.0.1"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81160037"],"award-info":[{"award-number":["81160037"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Healthcare Engineering"],"published-print":{"date-parts":[[2022,1,17]]},"abstract":"<jats:p>The mitochondrial GTPase mitofusin-2 (MFN2) gene can suppress the cell cycle and regulate cell proliferation in a number of cell types. However, its function in hepatic fibrosis remains largely unexplored. We attempted to understand the mechanism of MFN2 in hepatic stellate cell (HSC) proliferation and the development of hepatic fibrosis. Rat HSC-T6 HSC were cultured and transfected by adenovirus- (Ad-) Mfn2 or its negative control (NC) vector (Ad-green fluorescent protein (GFP)); a rat liver cirrhosis model was established via subcutaneous injection with carbon tetrachloride (CCl4). Seventy-two rats were randomly divided into four groups: CCl4, Mfn2, GFP, and NC. Ad-Mfn2 or Ad-GFP was transfected into the circulation via intravenous injection at day 1, 14, 28, 42, or 56 after the first injection of CCl4 in the Mfn2\/GFP groups. Biomarkers related to HSC proliferation and the development of hepatic fibrosis were detected using western blotting, hematoxylin-eosin and Masson staining, and immunohistochemistry. In vitro, Mfn2 interfered specifically with platelet-derived growth factor- (PDGF-) induced signaling pathway (phosphatidylinositol 3-kinase- (PI3K-) AKT), inhibiting HSC-T6 cell activation and proliferation. During the process of hepatic fibrosis in vivo, extracellular collagen deposition and the expression of fibrosis-related proteins increased progressively, while Mfn2 expression decreased gradually. Upregulating Mfn2 expression at the early stage of fibrosis impeded the process, triggered the downregulation of type I collagen, and antagonized the formation of factors associated with liver fibrosis. Mfn2 suppresses HSC proliferation and activation and exhibits antifibrotic potential in early-stage hepatic fibrosis. Therefore, it may represent a significant therapeutic target for eradicating hepatic fibrosis.<\/jats:p>","DOI":"10.1155\/2022\/6731335","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T19:20:09Z","timestamp":1642447209000},"page":"1-11","source":"Crossref","is-referenced-by-count":4,"title":["Mitofusin-2 Restrains Hepatic Stellate Cells\u2019 Proliferation via PI3K\/Akt Signaling Pathway and Inhibits Liver Fibrosis in Rats"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5605-9755","authenticated-orcid":true,"given":"Zhiping","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China"},{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5401-5959","authenticated-orcid":true,"given":"Zeyu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China"},{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2731-4512","authenticated-orcid":true,"given":"Jiandong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China"},{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4690-0082","authenticated-orcid":true,"given":"Haifeng","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Meizhou People\u2019s Hospital, Meizhou Hospital Affiliate to Sun Yat-Sen University, Meizhou 514021, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2713-9091","authenticated-orcid":true,"given":"Xianhua","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Endoscopy, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3599-1337","authenticated-orcid":true,"given":"Changku","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Affiliated Hangzhou First People\u2019s Hospital,School of Medicine, Zhejiang University, Hangzhou 310006, Zhejiang Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2098-218X","authenticated-orcid":true,"given":"Yunle","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China"},{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510650, Guangdong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1097\/mcc.0000000000000067"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1571295"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104720"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2003.50012"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2018.00150"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20853"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2014.10.014"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI37581"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20246314"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308325"},{"key":"11","first-page":"833","article-title":"The role of hypertension-related gene in aortic vascular smooth muscle cells from mice and rats","volume":"114","author":"G. 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