SOX9 promotes the progression of liver fibrosis by regulating hepatic stellate cells activation and proliferation

Abstract

Abstract: Objective To explore the effect of SRY-Box Transcription Factor 9 (SOX9) gene on the activation and proliferation of hepatic stellate cells. Methods An experimental model of liver fibrosis were induced by intraperitoneally injection of 15% carbon tetrachloride (CCl4) or corn oil as a control treatment three times a week in mice. H&E staining and Masson staining were used to observe the morphologies of mouse liver fibrosis. Real-time Quantitative PCR (qPCR) was used to detect the relative mRNA expression of SOX9, α-smooth muscle actin (α-SMA), and collagen type 1 (Col1) in the mouse liver. Transforming growth factor-β1 (TGFβ1) was used to induce hepatic stellate cell line LX2 activation, and qPCR was used to detect the relative mRNA expression of SOX9, α-SMA, Col1, Cyclin D1, and proliferating cell nuclear antigen (PCNA) genes with different treatments. Results By H&E and Masson staining it was shown that the liver fibrosis model was constructed successfully. The qPCR results showed that SOX9 gene was significantly upregulated in the liver of fibrotic mice, along with over-expressions of α-SMA and Col1, the main marker genes of hepatic stellate cells activation. The expression of SOX9 was tested to be significantly up-regulated in TGFβ1 stimulated LX2 cells. After knocking down of SOX9, the expressions of α-SMA, Col1, Cyclin D1 and PCNA were significantly decreased, and the activation and proliferation of LX-2 cells were significantly inhibited. Conclusion The expression of SOX9 is significantly increased in the mice livers with fibrogenesis. Knocking down of SOX9 can significantly reduce the hepatic stellate cells activation. SOX9 may therefore become a target for the treatment of liver fibrosis.

Key words: SRY-related high mobility group-box gene 9(SOX9), Hepatic stellate cells, Liver fibrosis

XIONG Min-li, GONG Xiao-yuan, WAN Shu-qi, LUO Sheng-zheng. SOX9 promotes the progression of liver fibrosis by regulating hepatic stellate cells activation and proliferation[J]. Chinese Hepatolgy, 2024, 29(2): 174-177.

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