{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T00:57:58Z","timestamp":1794013078942,"version":"4.8.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Liver fibrosis is reversible. Cholestasis is an important factor causing liver fibrosis. However, there are currently no effective anti-fibrotic drugs for cholestatic liver fibrosis in clinical practice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>mRNA sequencing was performed using mouse bile duct ligation (BDL) of liver tissue, and RT-qPCR was used to screen for the target gene REDD1. Immunohistochemistry was used to detect the expression of REDD1, CD68, \u03b1-SMA, and PI3K\/AKT\/mTOR signaling pathways in primary biliary cholangitis (PBC) patient liver tissue. Subsequently, adenovirus mediated REDD1 was transfected into mouse liver tissue via tail vein to evaluate its therapeutic effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RNA sequencing revealed REDD1 was significantly upregulated in BDL-induced fibrotic liver tissue. REDD1 expression correlated positively with \u03b1-SMA and CD68 in PBC patients, suggesting its involvement in fibrogenesis. However, REDD1 overexpression ameliorated BDL-induced liver injury, reduced serum ALT\/AST levels, and decreased collagen deposition, as evidenced by histological and molecular analyses (\u03b1-SMA and collagen I), indicating that REDD1 exhibited compensatory elevation in liver fibrosis. Additionally, PI3K\/AKT\/mTOR pathway was involved in the improvement of liver fibrosis by REDD1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings highlight REDD1 as a potential therapeutic target for liver fibrosis, acting probably through modulation of the PI3K\/AKT\/mTOR pathway to mitigate fibrotic processes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1628260","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T05:42:12Z","timestamp":1758692532000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["REDD1 attenuates cholestatic liver fibrosis and suppresses PI3K\/AKT\/mTOR 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