{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:28:57Z","timestamp":1790947737669,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003500","name":"Department of Surgery, Oncology and Gastroenterology, University of Padova","doi-asserted-by":"publisher","award":["BIRD198827\/19"],"award-info":[{"award-number":["BIRD198827\/19"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Liver fibrosis is a common and reversible feature of liver damage associated with many chronic liver diseases, and its onset is influenced by sex. In this study, we investigated the mechanisms of liver fibrosis and regeneration, focusing on understanding the mechanistic gaps between females and males. We injected increasing doses of carbon tetrachloride into female and male mice and maintained them for a washout period of eight weeks to allow for liver regeneration. We found that male mice were more prone to developing severe liver fibrosis as a consequence of early chronic liver damage, supported by the recruitment of a large number of Ly6Chigh MoM\u03c6s and neutrophils. Although prolonged liver damage exacerbated the fibrosis in mice of both sexes, activated HSCs and Ly6Chigh MoM\u03c6s were more numerous and active in the livers of female mice than those of male mice. After eight weeks of washout, only fibrotic females reported no activated HSCs, and a phenotype switching of Ly6Chigh MoM\u03c6s to anti-fibrogenic Ly6Clow MoM\u03c6s. The early stages of liver fibrosis mostly affected males rather than females, while long-term chronic liver damage was not influenced by sex, at least for liver fibrosis. Liver repair and regeneration were more efficient in females than in males.<\/jats:p>","DOI":"10.3390\/ijms242216452","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T09:10:38Z","timestamp":1700212238000},"page":"16452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Sex Drives Functional Changes in the Progression and Regression of Liver Fibrosis"],"prefix":"10.3390","volume":"24","author":[{"given":"Katia","family":"Sayaf","sequence":"first","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Zanotto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-8227","authenticated-orcid":false,"given":"Daniela","family":"Gabbia","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafne","family":"Alberti","sequence":"additional","affiliation":[{"name":"Laboratory of Synthetic Immunology, Department of Surgery Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"},{"name":"Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Pasqual","sequence":"additional","affiliation":[{"name":"Laboratory of Synthetic Immunology, Department of Surgery Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy"},{"name":"Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Zaramella","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, 35131 Padova, Italy"},{"name":"Gastroenterology Unit, Veneto Institute of Oncology IOV-IRCCS, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7206-9117","authenticated-orcid":false,"given":"Alberto","family":"Fantin","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Veneto Institute of Oncology IOV-IRCCS, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6398-8237","authenticated-orcid":false,"given":"Sara","family":"De Martin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4127-8941","authenticated-orcid":false,"given":"Francesco Paolo","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology and Gastroenterology, University of Padova, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Roehlen, N., Crouchet, E., and Baumert, T.F. 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