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. 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.