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Updated: Jan 15, 2026
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
REDD1 attenuates cholestatic liver fibrosis and suppresses PI3K/AKT/mTOR pathway
Xiaonan Li1, Xin Liu2, Xinrui Shi2
1Department of Radiotherapy, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
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.
Insights
Liver fibrosis, often caused by cholestasis, lacks effective treatments. This study found that REDD1 upregulation surprisingly protected against liver fibrosis by modulating the PI3K/AKT/mTOR pathway, suggesting REDD1 as a therapeutic target.
Area of Science:
- Hepatology
- Molecular Biology
- Fibrosis Research
Background:
- Liver fibrosis is a significant health concern, particularly when associated with cholestasis.
- Current therapeutic options for cholestatic liver fibrosis are limited.
- Understanding the molecular mechanisms underlying liver fibrosis is crucial for developing new treatments.
Purpose of the Study:
- To investigate the role of the gene REDD1 in liver fibrosis.
- To explore REDD1 as a potential therapeutic target for cholestatic liver fibrosis.
Main Methods:
- mRNA sequencing and RT-qPCR were used to identify REDD1 in a mouse model of bile duct ligation (BDL).
- Immunohistochemistry analyzed REDD1, CD68, α-SMA, and PI3K/AKT/mTOR pathway markers in primary biliary cholangitis (PBC) patient liver tissue.
- Adenovirus-mediated REDD1 transfection was employed to assess therapeutic effects in vivo.
Main Results:
- REDD1 was significantly upregulated in BDL-induced fibrotic liver tissue.
- REDD1 expression positively correlated with fibrotic markers (α-SMA, CD68) in PBC patients.
- REDD1 overexpression ameliorated liver injury, reduced liver enzymes (ALT/AST), and decreased collagen deposition in BDL mice, implicating a compensatory role.
Conclusions:
- REDD1 exhibits a protective effect against liver fibrosis, likely through the PI3K/AKT/mTOR pathway.
- REDD1 represents a promising therapeutic target for mitigating liver fibrosis, particularly in cholestatic conditions.
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