{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T15:13:41Z","timestamp":1777734821357,"version":"3.51.4"},"reference-count":80,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Zearalenone (ZEA) is a mycotoxin widely present in cereals, feeds, and foods, posing a persistent threat to human and animal health. Hepatic fibrosis is a pathological process characterized by excessive extracellular matrix (ECM) deposition. Chronic liver injury caused by sustained oxidative stress can initiate the development of early hepatic fibrosis. However, whether liver injury induced by ZEA can trigger hepatic stellate cell (HSC) activation and promote early profibrotic responses remains unclear. The aim of this study was to assess whether ZEA-induced liver injury promotes HSC activation and early profibrotic responses. To address this, we established a BALB\/c mouse exposure model and used the murine HSC line (JS-1) for in vitro validation. The results showed that ZEA exposure caused structural damage in hepatic tissue and produced an incomplete bridging pattern of collagen thickening suggestive of an early profibrotic tendency. ZEA shaped a proinflammatory microenvironment by activating the I\u03baB\u03b1\/NF-\u03baB axis and induced the TGF-\u03b21\/Smad2\/3 pathway, accompanied by Smad7 suppression, thereby promoting HSC activation and the expression of fibrosis-related genes. ZEA also altered autophagy-related markers in liver tissue and JS-1 cells. Pharmacological inhibition with chloroquine partially attenuated ZEA-induced upregulation of \u03b1-SMA and collagen I\/III, suggesting that autophagy-related processes may be involved in ZEA-associated HSC activation and early ECM deposition. In summary, ZEA promotes HSC activation and early profibrotic changes in the liver and is associated with inflammatory activation, TGF-\u03b21\/Smad signaling, and altered autophagy-related activity. These findings provide a basis for further investigation into the mechanisms underlying ZEA-induced early profibrotic remodeling in the liver.<\/jats:p>","DOI":"10.3390\/biom16050644","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:34:42Z","timestamp":1777458882000},"page":"644","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Zearalenone Promotes Hepatic Stellate Cell Activation and Early Profibrotic Tendency in the Liver"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8356-800X","authenticated-orcid":false,"given":"Lige","family":"Bao","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongze","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxin","family":"Bao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yitong","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunli","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyong","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1779-1190","authenticated-orcid":false,"given":"Jichang","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Janik, E., Niemcewicz, M., Ceremuga, M., Stela, M., Saluk-Bijak, J., Siadkowski, A., and Bijak, M. 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