Mechanism of FXR alleviating the liver fibrosis by regulating perilipin 5.

Autor: HUANG Xiao-xia, ZHENG Zhi-min, PANG Bi-ying, HUANG Na-na, LI Xin, XIONG Wen-ting, KONG Bo, LIU Ji-sheng
Předmět:
Zdroj: Journal of Hainan Medical University; Jun2023, Vol. 29 Issue 12, p10-17, 8p
Abstrakt: Objective: To investigate the regulatory mechanism in liver fibrosis progression by nuclear receptor of farnesoid X receptor (FXR) and the lipid droplet-associated protein of perilipin 5 (PLIN5). Methods: FXR response element (FXRE) upstream of PLIN5 gene was found by bioinformatics, and confirmed by a dual luciferase reporter gene system; a hepatic fibrosis model based on human hepatic stellate cell LX-2 was established by induction of transforming growth factor-β1 (TGF-β1); mRNA and protein levels of α-smooth muscle actin (α-SMA) and collagen I were measured by qPCR and Western blot after transient overexpression of FXR or PLIN5; Oil red O staining was used to study the formation of lipid droplets. Results: The promoter region of the PLIN5 gene contained a known reverse repeats-1 (IR-1); the gene expression of PLIN5 in LX-2 cells was up-regulated after FXR activation (P<0.01); overexpression of PLIN5 promoted the formation of lipid droplets and significantly reduced the TGF-β1 induced fibrosis gene expression (P<0.05); FXR activation showed no effects on the inhibition of LX-2 cells activation. Conclusion: Overexpression of PLIN5 promotes the formation of lipid droplets and inhibits activation of LX-2 cells. FXR might bind to the FXRE site upstream of PLIN5 gene and regulate its gene expression. In summary, FXR may prevent liver fibrosis progression partially by regulating lipid droplet-associated protein of PLIN5. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index