MicroRNA 27b promotes cardiac fibrosis by targeting the FBW7/Snail pathway
| Autor: | Xiaochun Lu, Zhihong Lu, Qiang Fu, Shitang Ma, Xiao Fu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Aging F-Box-WD Repeat-Containing Protein 7 Heart Diseases Cardiac fibrosis cardiac fibrosis Rats Sprague-Dawley In vivo Fibrosis microRNA medicine Animals Humans MTT assay Cell Proliferation Chemistry Myocardium microRNA 27b Cell Biology Fibroblasts medicine.disease Angiotensin II Rats MicroRNAs Snail Cancer research FBW7 Myocardial fibrosis Snail Family Transcription Factors Ligation Signal Transduction Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Our study aspires to understand the impact of miR-27b on myocardial fibrosis as well as its functional mechanism. 12 days post the ligation of coronary artery in rats, the expression of miR-27b in the peri-infarction region was elevated. Treating cultivated rat neonatal cardiac fibroblasts (CFs) with angiotensin II (AngII) also enhanced the miR-27b expression. Forced expression of miR-27b promoted the proliferation and collagen production in rat neonatal CFs, as revealed by cell counting, MTT assay, and quantitative reverse transcription-polymerase chain reaction. FBW7 was found to be the miR-27b's target since the overexpression of miR-27b reduced the transcriptional level of FBW7. The enhanced expression of FBW7 protein abrogated the effects of miR-27b in cultured CFs, while the siRNA silence of FBW7 promoted the pro-fibrosis activity of AngII. As to the mechanism, we found that the expression of FBW7 led to the degradation of Snail, which is an important regulator of cardiac epithelial-mesenchymal transitions. Importantly, inhibition of miR-27b abrogated the coronary artery ligation (CAL) induced cardiac fibrosis in vivo, suggesting that it might be a potential target for the treatment of fibrosis associated cardiac diseases. |
| Databáze: | OpenAIRE |
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