MicroRNA-26b-5p Inhibits Mouse Liver Fibrogenesis and Angiogenesis by Targeting PDGF Receptor-Beta
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 (MCD...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Book |
| Published: |
Elsevier,
2019-06-01T00:00:00Z.
|
| Subjects: | |
| Online Access: | Connect to this object online. |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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: microRNA-26b-5p, long non-coding RNA maternally expressed gene 3, bone marrow mesenchymal stromal cell, platelet-derived growth factor receptor-beta, angiogenesis, liver fibrosis |
|---|---|
| Item Description: | 2162-2531 10.1016/j.omtn.2019.02.014 |