Tai Yang, Zhao Chong, Lan Tian, Zhang Linhao, Xiao Yang, Tong Huan, Liu Rui, Tang Chengwei, Gao Jinhang
Laboratory of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
Front Genet. 2021 Jul 22;12:706341. doi: 10.3389/fgene.2021.706341. eCollection 2021.
Liver fibrosis results from the imbalance between extracellular matrix (ECM) production and degradation, which is a common pathological consequence of various chronic liver diseases. Although many miRNAs have been reported in liver fibrosis progression, miRNA-mRNA interactions in its reversal process remain to be elucidated. In the current study, we performed an integrated analysis of miRNA and mRNA expression profiles in the mouse model with the spontaneous reversal potency of liver fibrosis. A total of 102 miRNA and 2,845 mRNAs showed significant differential expression in reversal mice compared to fibrotic mice. Moreover, 3,769 putative negatively correlated miRNA-mRNA pairs were revealed to be potentially implicated in the biological function regulation of small molecule metabolism and ECM organization. By integrating miRNA-mRNA regulatory networks, mmu-miR-1843a-5p, mmu-miR-193a-5p, mmu-miR-194-2-3p, and mmu-miR-30c-2-3p were identified as lysyl oxidases-specific miRNAs that were correlated with fibrosis reversal. Our results provided potential candidate targets for the treatment of liver fibrosis.
肝纤维化是由细胞外基质（ECM）产生与降解之间的失衡所致，这是各种慢性肝病常见的病理后果。尽管在肝纤维化进展过程中已报道了许多微小RNA（miRNA），但其逆转过程中的miRNA-信使核糖核酸（mRNA）相互作用仍有待阐明。在本研究中，我们对具有肝纤维化自发逆转能力的小鼠模型中的miRNA和mRNA表达谱进行了综合分析。与纤维化小鼠相比，共有102个miRNA和2845个mRNA在逆转小鼠中表现出显著差异表达。此外，发现3769个推定的负相关miRNA-mRNA对可能参与小分子代谢和ECM组织的生物学功能调节。通过整合miRNA-mRNA调控网络，鉴定出mmu-miR-1843a-5p、mmu-miR-193a-5p、mmu-miR-194-2-3p和mmu-miR-30c-2-3p为与纤维化逆转相关的赖氨酰氧化酶特异性miRNA。我们的结果为肝纤维化治疗提供了潜在的候选靶点。
