AIMS Liver fibrosis is a chronic liver disease characterized by hepatic stellate cell (HSC) activation. Peroxisome proliferator-activated receptor gamma (PPARγ) play an important role in HSC activation. This study aimed to investigate the role of PPARγ in the progression of human hepatic fibrosis and the mechanism by which microRNA-942 regulates HSC activation. METHODS 70 chronic hepatitis B (CHB) patients liver tissues were used to assess PPARγ, α-SMA and miR-942 levels by immunoblot and real-time PCR. Human primary HSCs or LX2 cells were used to perform multiple molecular experiments based on the transfection of small interfering RNA (siRNA) or co-transfection of microRNA inhibitor. Site-directed mutagenesis and luciferase reporter assays were used to identify miR-942 targets. miR-942 expression and localization in hepatic fibrosis and co-localization between α-SMA were determined by fluorescence in situ hybridization (FISH). KEY FINDINGS The mRNA expression of PPARγ was decreased in activated HSCs and CHB patients with liver fibrosis, which was negatively correlated with F stage and α-SMA. miR-942 negatively regulates PPARγ expression via targeting the PPARγ 3'UTR. Inhibiting PPARγ promoted TGFβ1 induced HSC activation, and this effect was blocked after inhibiting the miR-942. Moreover, miR-942 was mainly expressed in fibrous septa and negatively correlated with PPARγ in liver fibrosis. SIGNIFICANCE PPARγ targeting by miR-942 and decreasing HSC activation in human hepatic fibrosis. Hence, regulating PPARγ may be a promising therapeutic strategy for hepatic fibrosis.

中文翻译：

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过氧化物酶体增殖物激活受体γ抑制miR-942在慢性乙型肝炎肝纤维化中调节的肝星状细胞激活。

AIMS肝纤维化是一种以肝星状细胞（HSC）激活为特征的慢性肝病。过氧化物酶体增殖物激活受体γ（PPARγ）在HSC激活中起重要作用。这项研究旨在研究PPARγ在人类肝纤维化进程中的作用以及microRNA-942调节HSC激活的机制。方法采用免疫印迹和实时荧光定量PCR方法，对70例慢性乙型肝炎（CHB）患者肝组织进行PPARγ，α-SMA和miR-942水平评估。基于小干扰RNA（siRNA）的转染或microRNA抑制剂的共转染，使用人类原代HSC或LX2细胞进行多分子实验。定点诱变和荧光素酶报告基因分析被用于鉴定miR-942靶标。通过荧光原位杂交（FISH）确定miR-942在肝纤维化中的表达和定位以及α-SMA之间的共定位。主要发现激活的HSCs和CHB肝纤维化患者中PPARγ的mRNA表达降低，这与F期和α-SMA呈负相关。miR-942通过靶向PPARγ3'UTR负调控PPARγ的表达。抑制PPARγ促进TGFβ1诱导HSC活化，并且在抑制miR-942后这种作用被阻断。而且，miR-942主要在纤维间隔中表达，与肝纤维化中的PPARγ呈负相关。意义miR-942靶向PPARγ并降低人肝纤维化中的HSC活化。因此，调节PPARγ可能是肝纤维化的有前途的治疗策略。