The Research About The Effect And Mechanism Of Brg1 On Liver Fibrosis

Objectives:To find the role and mechanism of Brahma-related gene 1?Brg1?on the liver fibrosisMethods:1.To analyze the difference of Brg1 expression between normal liver tissue and liver fibrosis tissue?clinical samples of patients with liver cirrhosis and liver cancer?.2.Brg1 was overexpressed and underexpressed in activated hepatic stellate cells,and the differential expression of genes related to hepatic fibrosis was detected.3.Brg1 was overexpressed and underexpressed in human hepatic stellate cells LX-2,and the expression of key proteins in TGF/Smad pathway was detected.4.Chronic liver injury animal model was established in vitro,then the change trend of liver fibrosis and the expression of key proteins in TGF/Smad pathway were detected after low expression of BRG1.5.To detect the difference of Brg1 expression between normal and fibrotic tissues by collecting clinical samples of liver cirrhosis and liver cancer.Results:1.The expression of Brg1 in normal and fibrotic tissues was detected in TCGA and GEO databases,which showed that the expression of Brg1 in fibrotic tissues was significantly increased.2.Brg1-specific siRNA and high expression of plasmid were transfected into LX-2cells,low and high expression of?-SMA and Colla1 both in protein or mRNA can be detected by Western blot and Real-time PCR.3.Brg1 protein can bind to Smad3 protein.After low expression of Brg1,the transcription level of?-SMA and Colla1 decreased.4.Low expression of Brg1 can reduce the degree of liver fibrosis.5.In CCl₄-induced fibrosis mice model,low expression of Brg1 significantly improved fibrosis.6.Brg1 expression was significantly increased in clinical specimens of liver cirrhosis and hepatocellular carcinoma.Conclusion:Brg1 can up-regulate the expression of?-SMA and Colla1 through TGF/Smad-SMA/Colla1 signaling pathway,thus promoting fibrosis.