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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253119300447 |
| _version_ | 1819259018491723776 |
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| author | Le Yang Chengbin Dong Jingjing Yang Lin Yang Na Chang Changbo Qi Liying Li |
| author_facet | Le Yang Chengbin Dong Jingjing Yang Lin Yang Na Chang Changbo Qi Liying Li |
| author_sort | Le Yang |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-23T19:03:20Z |
| format | Article |
| id | doaj.art-e4fb1c1bd9c446f89071c99a4a4445a5 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-23T19:03:20Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-e4fb1c1bd9c446f89071c99a4a4445a52022-12-21T17:34:40ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-06-0116206217MicroRNA-26b-5p Inhibits Mouse Liver Fibrogenesis and Angiogenesis by Targeting PDGF Receptor-BetaLe Yang0Chengbin Dong1Jingjing Yang2Lin Yang3Na Chang4Changbo Qi5Liying Li6Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, ChinaDepartment of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, ChinaDepartment of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, ChinaDepartment of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, ChinaDepartment of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, ChinaDepartment of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, ChinaDepartment of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China; Corresponding author: Liying Li, Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, China.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 fibrosishttp://www.sciencedirect.com/science/article/pii/S2162253119300447 |
| spellingShingle | Le Yang Chengbin Dong Jingjing Yang Lin Yang Na Chang Changbo Qi Liying Li MicroRNA-26b-5p Inhibits Mouse Liver Fibrogenesis and Angiogenesis by Targeting PDGF Receptor-Beta Molecular Therapy: Nucleic Acids |
| title | MicroRNA-26b-5p Inhibits Mouse Liver Fibrogenesis and Angiogenesis by Targeting PDGF Receptor-Beta |
| title_full | MicroRNA-26b-5p Inhibits Mouse Liver Fibrogenesis and Angiogenesis by Targeting PDGF Receptor-Beta |
| title_fullStr | MicroRNA-26b-5p Inhibits Mouse Liver Fibrogenesis and Angiogenesis by Targeting PDGF Receptor-Beta |
| title_full_unstemmed | MicroRNA-26b-5p Inhibits Mouse Liver Fibrogenesis and Angiogenesis by Targeting PDGF Receptor-Beta |
| title_short | MicroRNA-26b-5p Inhibits Mouse Liver Fibrogenesis and Angiogenesis by Targeting PDGF Receptor-Beta |
| title_sort | microrna 26b 5p inhibits mouse liver fibrogenesis and angiogenesis by targeting pdgf receptor beta |
| url | http://www.sciencedirect.com/science/article/pii/S2162253119300447 |
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