1. 20-Hydroxytetraenoic acid induces hepatic fibrosis via the TGF-β1/Smad3 signaling pathway.
- Author
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Li, Biao, Ma, Yuchen, Tan, Lina, Ren, Huan, Wu, Lifang, Su, Qian, Song, Jue, Chen, Wei, Gong, Peng, and Jin, Yong
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HEPATIC fibrosis , *CELLULAR signal transduction , *ARACHIDONIC acid , *LIVER cells , *CARBON tetrachloride - Abstract
Hepatic fibrosis is caused by excessive accumulation of extracellular matrix (ECM) due to repeated liver injury. Hepatic stellate cells (HSCs) play a key role in the pathogenesis and progression of hepatic fibrosis. A study showed that CYP4A14 gene defect can inhibit hepatic fibrosis, but the specific mechanism was not clear. In this experiment, patients with hepatic fibrosis, LX-2 cells (a human HSCs line), and mice with liver fibrosis induced by carbon tetrachloride (CCl 4) were used to study the effect of 20-Hydroxytetraenoic acid (20-HETE), one of the main metabolites of arachidonic acid (AA) catalyzed by CYP4A enzyme, on hepatic fibrosis and its mechanism. Our experimental results showed that the 20-HETE of patients with hepatic fibrosis is significantly higher than that of normal people and is closely related to the degree of fibrosis. 20-HETE could induce activation of LX-2 cells and 20-HETE antagonist could inhibit the induction of 20-HETE. 20-HETE was significantly increased in CCl 4 -induced liver fibrosis mice and inhibition of 20-HETE production could attenuate hepatic fibrosis. 20-HETE induced hepatic fibrosis mainly via the TGF- β1/Smad3 signal pathway. In conclusion, the results suggest that 20-HETE plays an important role in hepatic fibrosis and may be a possible target for the clinical treatment of hepatic fibrosis. [Display omitted] • 20-HETE is highly expressed in patients with hepatic fibrosis. • 20-HETE is strongly correlated with the stages of fibrosis in patients with hepatic fibrosis. • 20-HETE promotes hepatic stellate cell activation. • 20-HETE aggravated CCl 4 -induced hepatic fibrosis in mice through the TGF-β1/Smad3 signaling pathway. • 20-HETE is expected to be a new therapeutic target for hepatic fibrosis. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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