microRNA、细胞自噬与肝纤维化

近年来研究发现微小RNA（microRNA）在肝纤维化发生中起到重要调节作用,明晰miR表达谱的差别有助于揭示肝纤维化发生的分子调节机制、发现肝纤维化诊断的分子标志、并有助于发现新的治疗策略。此外研究还发现自噬（autophagy）信号在肝星状细胞（HSC）激活中起到重要作用,静息HSC通过自噬使含维生素A酯的脂滴释放和被利用,以此产生能量来驱动HSC的活化过程。该发现是肝纤维化发生机制的重要补充。

Recent perspectives on mechanisms of liver fibrogenesis: microRNA and cell autophagy

Liver fibrogenesis remains a significant outcome of chronic liver disease and etiologic factors of progression to end-stage liver cirrhosis.In recent years,the collective research efforts on the cellular and molecular mechanisms underlying this pathogenic condition have uncovered important regulatory roles for microRNAs（miRs） and autophagy signaling.In particular,miR-mediated silencing of target gene expression has been shown to regulate activation of the hepatic stellate cells（HSCs）,which are the main source of the aberrantly synthesized and deposited extracellular matrix proteins.While several specific miRs have been identified and functionally characterized under conditions of liver fibrosis,such as miR-29b and its effects on type I collagen and TGFβ signaling,the entire panel of miRs and their contribution to the pathogenic process remains to be fully elucidated.Autophagy signaling has also been shown to regulate HSC activation.In particular,autophagy signaling stimulates the release of retinol ester and triglyceride containing lipid droplets from quiescent HSCs,and the energy generated from these fatty acids＇ breakdown causes HSC activation.In this review,the current knowledge on each of these newly recognized pathogenic mechanisms is summarized.By expanding our knowledge of the fibrogenesis-related processes involving miRs and/or autophagy signaling pathways/factors,effective molecular biomarkers may be identified to improve diagnosis,and novel therapeutic strategies may be developed for clinical applications.