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Abstract：
Liver fibrosis is a persistent damage repair response triggered by various injury factors, which leads to an abnormal accumulation of extracellular matrix within liver tissue samples. The current clinical treatment of liver fibrosis is currently ineffective; therefore, elucidating the mechanism of liver fibrogenesis is of significant importance. Herein, the function and related mechanisms of lncRNA Snhg12 within hepatic fibrosis were investigated. Snhg12 expression was shown to be increased in mouse hepatic fibrotic tissue samples, and Snhg12 knockdown suppressed hepatic pathological injury and down-regulated the expression levels of fibrosis-associated proteins. Mechanistically, Snhg12 played a role in the early activation of mouse hepatic stellate cells (mHSCs) based on bioinformatics analysis, and Snhg12 was positively correlated with Igfbp3 expression. Further experimental results demonstrated that Snhg12 knockdown impeded mHSCs proliferation and activation and also downregulated the protein expression of Igfbp3. Snhg12 could interact with IGFBP3 and boost its protein stability, and overexpression of Igfbp3 partially reversed the inhibition of mHSCsproliferation and activation by the knockdown of Snhg12. In conclusion, LncRNA Snhg12 mediates liver fibrosis by targeting IGFBP3 and promoting its protein stability, thereby promoting mHSC proliferation and activation. Snhg12 has been identified as an underlying target for treating liver fibrosis.
摘要：
肝纤维化是由多种损伤因素引发的持续性损伤修复反应,这导致肝脏组织样本内细胞外基质的异常积累。目前临床上对肝纤维化的治疗是无效的,因此,阐明肝纤维化发生的机制具有重要意义。在这里，研究了lncRNASnhg12在肝纤维化中的功能和相关机制。Snhg12表达在小鼠肝纤维化组织样品中增加，Snhg12基因敲除抑制肝脏病理损伤并下调纤维化相关蛋白的表达水平。机械上,基于生物信息学分析,Snhg12在小鼠肝星状细胞(mHSCs)的早期活化中发挥作用,Snhg12与Igfbp3表达呈正相关。进一步的实验结果表明，Snhg12敲低会阻碍mHSCs的增殖和激活，并下调Igfbp3的蛋白表达。Snhg12可以与IGFBP3相互作用，增强其蛋白稳定性，Igfbp3的过表达通过敲低Snhg12部分逆转了mHSCs增殖和激活的抑制。总之,LncRNASnhg12通过靶向IGFBP3并促进其蛋白稳定性介导肝纤维化,从而促进mHSC增殖和活化。Snhg12已被确定为治疗肝纤维化的潜在靶标。
