{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T07:21:05Z","timestamp":1780730465114,"version":"3.54.1"},"reference-count":62,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:00:00Z","timestamp":1699833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundations of China","award":["81703176"],"award-info":[{"award-number":["81703176"]}]},{"name":"Natural Science Foundations of China","award":["81972986"],"award-info":[{"award-number":["81972986"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Arsenic pollution is a global environmental concern. Arsenic-induced chronic liver injury and its irreversible outcomes, including liver cirrhosis and liver cancer, threaten the health of residents in arsenic-contaminated areas. Liver fibrosis is a reversible pathological stage in the progression of arsenic-induced chronic liver injury to cirrhosis and liver cancer. The aim of this study is to identify the epigenetic mechanism of arsenic-induced liver fibrosis based on the dedifferentiation of liver sinusoidal endothelial cells (LSECs). Rats were treated with 0.0, 2.5, 5.0, or 10.0 mg\/kg sodium arsenite for 36 weeks. Marked fibrotic phenotypes were observed in the rat livers, manifested by hepatic stellate cell activation and an increased extracellular matrix, as well as the deposition of collagen fibers. The reduced fenestrations on the cells\u2019 surface and the increased expression of the dedifferentiation marker CD31 corroborated the LSECs\u2019 dedifferentiation in the liver tissue, which was also found to be significantly associated with fibrotic phenotypes. We further revealed that arsenic exposure could inhibit the enrichment of histone H3 lysine 18 acetylation (H3K18ac) in the promoters of Fcgr2b and Lyve1, two key genes responsible for maintaining the differentiation phenotype of LSECs. This inhibition subsequently suppressed the genes\u2019 expression, promoting LSEC dedifferentiation and subsequent liver fibrosis. In conclusion, arsenic can trigger liver fibrosis by inhibiting H3K18ac-dependent maintenance of LSEC differentiation. These findings uncover a novel mechanism of arsenic-induced liver fibrosis based on a new insight into epigenetically dependent LSEC dedifferentiation.<\/jats:p>","DOI":"10.3390\/toxics11110928","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T08:44:27Z","timestamp":1699865067000},"page":"928","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Suppressed Histone H3 Lysine 18 Acetylation Is Involved in Arsenic-Induced Liver Fibrosis in Rats by Triggering the Dedifferentiation of Liver Sinusoidal Endothelial Cells"],"prefix":"10.3390","volume":"11","author":[{"given":"Fang","family":"Hu","sequence":"first","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang 550025, China"},{"name":"Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-Constructed by the Province and Ministry, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingcheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang 550025, China"},{"name":"Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-Constructed by the Province and Ministry, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Peng","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang 550025, China"},{"name":"Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-Constructed by the Province and Ministry, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Ma","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang 550025, China"},{"name":"Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-Constructed by the Province and Ministry, Guizhou Medical University, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111215","DOI":"10.1016\/j.mad.2020.111215","article-title":"SIRT1 and aging related signaling pathways","volume":"187","author":"Chen","year":"2020","journal-title":"Mech. 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