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Updated: Dec 25, 2025

Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
The in vitro effects of phospholipase D1-mTOR axis in liver fibrogenesis
Yizhong Chang1, Lu Xia1, Meiyi Song1
1Department of Gastroenterology and Hepatology, Institution of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Aims:
The activation of hepatic stellate cells (HSCs) plays a central role in liver fibrosis progression. Phospholipase D (PLD) enzymes participate in multiple cellular activities. However, whether and how PLD regulates HSCs activation remain elusive.
Main Methods:
The expression of intrahepatic PLD1 and PLD2 was determined in CCl4-induced mouse liver fibrosis models by western blot and immunohistochemistry. Cell model of liver fibrogenesis was constructed using rat HSCs line (HSC-T6) treated with recombinant transforming growth factor β1 (TGFβ1). Fibrogenesis was evaluated on the aspects of proliferation, expression of pro-fibrogenic markers and migration. The effects mediated by PLD1-mTOR axis on TGFβ1-induced fibrogenesis were evaluated using HSC-T6 treated with small-molecular PLD1 inhibitors, PLD1-SiRNA, rapamycin (mTOR inhibitor) and MHY1485 (mTOR activator).
Key Findings:
Significant increase of PLD1, not PLD2 was documented in CCl4-induced cirrhotic compared to normal liver tissues. Suppression of PLD1 activities by PLD inhibitors or down-regulation of PLD1 expression in HSC-T6 could significantly restrain TGFβ1-induced fibrogenesis, as reflected by decreased cell proliferation and reduced expression of pro-fibrogenic markers. Besides, either PLD1 inhibitor or PLD1-SiRNA significantly inhibited mTOR activity of HSC-T6. Moreover, PLD1 inhibitors not only exhibited similar effects with rapamycin in TGFβ1-induced fibrogenesis, but also blunted MHY1485 enhanced cell proliferation of HSC-T6.
Significance:
The PLD1-mTOR axis of HSCs could be therapeutically targeted in advanced liver fibrosis.
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