4.6 Article

Integrated Analysis of Hepatic miRNA and mRNA Expression Profiles in the Spontaneous Reversal Process of Liver Fibrosis

Journal

FRONTIERS IN GENETICS
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2021.706341

Keywords

miRNA; mRNA; liver fibrosis; spontaneous reversal; extracellular matrix; lysyl oxidase

Funding

  1. National Natural Science Foundation of China [81670551, U1702281, 81873584, 82000613, 82000574]
  2. National Key R&D Program of China [2017YFA0205404]
  3. Sichuan Science and Technology Program [2020YJ0084, 2021YFS0147]
  4. West China Hospital, Sichuan University [2019HXBH074]

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Liver fibrosis results from the imbalance between ECM production and degradation, with many miRNAs being involved in its progression. This study identified specific miRNAs correlated with fibrosis reversal in a mouse model and provided potential candidate targets for liver fibrosis treatment. The integrated analysis of miRNA and mRNA expression profiles revealed significant differential expression and putative regulatory networks related to small molecule metabolism and ECM organization.
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.

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