Integrated analysis of hepatic miRNA and mRNA expression profiles in the spontaneous recovery of liver fibrosis [miRNA]

Liver fibrosis, results from the imbalance between extracellular matrix (ECM) production and degradation, is a common pathological consequence of various chronic liver diseases. Although a large number of miRNAs have been reported in liver fibrosis progression, miRNA-mRNA interactions involved in its reversal process remain to be fully elucidated. In the current study, we performed an integrated analysis of miRNA and mRNA expression profiles in a hepatic fibrosis recovery mouse model induced by thioacetamide. A total of 102 miRNA and 2,845 mRNAs showed significant differential expression in recovery 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 oxidase-specific miRNAs that were associated with the pathogenesis of fibrosis recovery. Our results provide potential novel biomarkers and candidate targets for the treatment of liver fibrosis. Overall design: Liver fibrosis was induced by intraperitoneal injection of thioacetamide (TAA) for 8 weeks. Control mice received the same volume of normal saline (NS). Liver fibrosis recovery model (Recovery) was established via 8-week TAA injection and then withdrew the repeated liver damages, following by spontaneous recovery for additional 8 weeks. miRNA expression profile was performed in the liver tissues of TAA-fibrotic mice, recovery mice and control mice.