MicroRNA-26b-5p Inhibits Mouse Liver Fibrogenesis and Angiogenesis by Targeting PDGF Receptor-Beta

Le Yang; Chengbin Dong; Jingjing Yang; Lin Yang; Na Chang; Changbo Qi; Liying Li

doi:10.1016/j.omtn.2019.02.014

MicroRNA-26b-5p Inhibits Mouse Liver Fibrogenesis and Angiogenesis by Targeting PDGF Receptor-Beta

Mol Ther Nucleic Acids. 2019 Jun 7:16:206-217. doi: 10.1016/j.omtn.2019.02.014. Epub 2019 Feb 26.

Authors

Le Yang¹, Chengbin Dong¹, Jingjing Yang¹, Lin Yang¹, Na Chang¹, Changbo Qi¹, Liying Li²

Affiliations

¹ Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China.
² Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China. Electronic address: liliying@ccmu.edu.cn.

Abstract

Here microRNAs (miRNAs) with potentially therapeutic effects were screened and explored during liver fibrogenesis and angiogenesis via targeting the important mediators. Chimera mice with EGFP⁺ bone marrow mesenchymal stromal cells (BMSCs) were fed with methionine-choline-deficient and high-fat (MCDHF) diet to induce liver injury. Increased expression of platelet-derived growth factor receptor-beta (PDGFR-β) was detected in MCDHF mice, with a positive correlation to fibrosis and angiogenesis markers. BMSCs contributed to the significant proportion of PDGFR-β⁺ cells in the fibrotic liver. MicroRNA-26b-5p (miR-26b-5p) was predicted to target PDGFR-β from three databases. The hepatic expression of miR-26b-5p was decreased in the fibrotic liver, with a negative correlation to PDGFR-β and fibrosis and angiogenesis markers. miR-26b-5p directly targeted PDGFR-β in TGF-β1-treated BMSCs by pull-down and lucifer reporter assays, which can be sponged by long non-coding RNA (lncRNA) maternally expressed gene 3 (lncMEG3). Microarray analysis revealed that miR-26b-5p overexpression affected a list of genes associated with fibrosis and angiogenesis. In vivo miR-26b-5p negatively regulated PDGFR-β expression and attenuated liver fibrosis and angiogenesis. Together, miR-26b-5p inhibits liver fibrogenesis and angiogenesis via directly targeting PDGFR-β and interacting with lncMEG3, which may represent an effective therapeutic strategy for liver fibrosis.

Keywords: angiogenesis; bone marrow mesenchymal stromal cell; liver fibrosis; long non-coding RNA maternally expressed gene 3; microRNA-26b-5p; platelet-derived growth factor receptor-beta.