ORIGINAL RESEARCH article
Front. Med.
Sec. Hepatobiliary Diseases
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1628260
REDD1 attenuates cholestatic liver fibrosis and suppresses PI3K/AKT/mTOR pathway
Provisionally accepted
- 1Shanxi Provincial People’s Hospital, Taiyuan, China
- 2First Hospital of Shanxi Medical University, Taiyuan, China
- 3Shanxi Medical University, Taiyuan, China
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Introduction: 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. Methods: 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, α-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. Results: RNA sequencing revealed REDD1 was significantly upregulated in BDL-induced fibrotic liver tissue. REDD1 expression correlated positively with α-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 (α-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. Conclusions: 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.
Keywords: Primary biliary cholangitis, bile duct ligation, liver fibrosis, REDD1, PI3K/AKT/mTOR
Received: 14 May 2025; Accepted: 05 Sep 2025.
Copyright: © 2025 Li, Liu, Shi, Li, Shuai, Huang, Liu and Ren. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Tingjuan Huang, Shanxi Medical University, Taiyuan, China
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