SOX9调控肝星状细胞活化与增殖促进肝纤维化进展

肝脏 ›› 2024, Vol. 29 ›› Issue (2): 174-177.

SOX9调控肝星状细胞活化与增殖促进肝纤维化进展

熊敏莉, 龚晓媛, 万舒淇, 罗声政

201620 上海对外经贸大学门诊部(熊敏莉);上海交通大学医学院附属第一人民医院消化科/消化内镜中心(龚晓媛,万舒淇,罗声政)

收稿日期:2023-11-08 出版日期:2024-02-29 发布日期:2024-03-18
通讯作者: 罗声政,Email:luoshengzheng2007@163.com
基金资助:
2021年度松江区科技攻关项目(21SJKJGG054)

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

XIONG Min-li¹, GONG Xiao-yuan², WAN Shu-qi², LUO Sheng-zheng²

1. Outpatient Department of Shanghai University of International Business and Economics, 201620 Shanghai, China;
2. Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 201620 Shanghai, China

Received:2023-11-08 Online:2024-02-29 Published:2024-03-18
Contact: LUO Sheng-Zheng,Email:luoshengzheng2007@163.com

摘要/Abstract

摘要： 目的探究SOX9基因对肝星状细胞活化与增殖的影响。方法通过每周三次腹腔注射15%的四氯化碳或玉米油构建肝纤维化及对照小鼠模型。HE染色、Masson染色观察小鼠肝纤维化造模情况,qPCR检测小鼠肝脏SOX9、α-SMA、Col1基因表达。用TGFβ1细胞因子诱导LX2细胞活化,qPCR检测LX2细胞活化状态及敲减SOX9基因后 SOX9、α-SMA、Col1、CyclinD1、PCNA基因mRNA表达。结果 HE、Masson染色表明肝纤维化模型成功构建。qPCR结果表示肝纤维化标志基因α-SMA(造模组:2.568±0.726,对照组:1.000±0.272, t=4.518, P=0.002)与Col1表达明显上升(造模组:3.125±0.775,对照组:1.000±0.398, t=5.454, P=0.001)。SOX9基因在纤维化的小鼠肝脏中也显著上升(造模组:1.986±0.634,对照组:1.000±0.288, t=3.126, P=0.014)。在活化的LX2细胞中SOX9基因表达显著上调(活化组:1.718±0.395,对照组:1.000±0.155, t=3.783, P=0.005),敲减SOX9基因后胶原合成基因α-SMA(敲减组:0.621±0.142 ,对照组:1.000±0.188, t=3.590, P=0.007)与Col1(敲减组:0.558±0.170 ,对照组:1.000±0.130, t=4.608, P=0.002)以及增殖相关基因CyclinD1(敲减组:0.614±0.106 ,对照组:1.000±0.166, t=4.392, P=0.002)和PCNA(敲减组:0.525±0.138,对照组:1.000±0.234, t=3.897, P=0.005)表达明显下降,肝星状细胞活化与增殖被明显抑制。结论 SOX9基因在肝纤维化小鼠肝脏中表达明显上升,敲减SOX9基因可以明显减轻肝星状细胞的活化,可能成为治疗肝纤维化的靶点。

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

熊敏莉, 龚晓媛, 万舒淇, 罗声政. SOX9调控肝星状细胞活化与增殖促进肝纤维化进展[J]. 肝脏, 2024, 29(2): 174-177.

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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