Micro-RNA 21Targets Dual Specific Phosphatase 8 to Promote Collagen Synthesis in High Glucose-Treated Primary Cardiac Fibroblasts

作者：Liu, Shulei; Li, Wenqi; Xu, Mingtong; Huang, Hui; Wang, Jingfeng; Chen, Xiaochao^*

来源：Canadian Journal of Cardiology, 2014, 30(12): 1689-1699.

DOI：10.1016/j.cjca.2014.07.747

• CARDIOMYOCYTE HYPERTROPHY
• MYOCARDIAL FIBROSIS
• MICRORNA-21
• ACTIVATION
• EXPRESSION
• PROTECTS
• FAILURE
• KINASES
• PATHWAY
• TARGET

Background: Micro-RNA 21 (miR-21) has been shown to contribute to cardiac fibrosis in many diseases. In this study we investigated the role of miR-21 in excessive production of collagen in diabetic cardiomyopathy. @@@ Methods: The proliferation rate of cardiac fibroblasts was analyzed by Western blot, Cell Counting Kit-8 kit (Dojindo Molecular Technologies, Kumamoto, Japan), and Cell-Light EdU Apollo 488 In Vitro Imaging Kit (RiboBio, Guangzhou, China). Real-time polymerase chain reaction and Western blotting were conducted to determine gene expression levels. A luciferase reporter assay was used to verify the interaction between miR-21 and the 3' untranslated region (3'UTR) of dual specific phosphatase 8 (DUSP8). @@@ Results: Our results show that high glucose promoted the proliferation and collagen synthesis of rat cardiac fibroblasts, which was accompanied by an increase of miR-21. Gain-of-function and loss-of-function assays confirmed that miR-21 mediated this effect, suggesting the crucial role of miR-21 in diabetic cardiomyopathy. Our study also identified a direct target of miR-21, DUSP8, which regulates cell proliferation and collagen synthesis in cardiac fibroblasts through p38 and c-Jun N-terminal kinase (JNK)/stress-activated kinase (SAPK) signalling. Our results show that miR-21 bound to the 3'UTR of DUSP8 post-transcriptionally repressed its expression. In addition, enforced expression of miR-21 activated the JNK/SAPK and p38 signalling pathways. @@@ Conclusions: Our study shows that miR-21 promotes high glucose-induced cardiac fibrosis through the JNK/SAPK and p38 signalling pathways by suppressing DUSP8 expression.

• 出版日期2014-12
• 单位中山大学