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Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
miR-155 regulates high glucose-induced cardiac fibrosis via the TGF-β signaling pathway
Dong Zhang1, Yongchun Cui1, Bin Li1
1Chinese Academy of Medical Sciences, Peking Union Medical College, National Centre for Cardiovascular Disease, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, Beijing Key Laboratory of Pre-Clinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, Beijing 100037, China. tangyue@fuwaihospital.org.
Abstract:
Cardiac fibrosis, as a pathological process, plays an important role in various cardiac diseases. microRNA-155 (miR-155) is one of the most important miRNAs, and previous studies have shown that it is a regulatory factor in various fibrotic diseases. However, the mechanism by which miR-155 affects myocardial fibrosis remains unclear. In this study, we aim to establish the biological function of miR-155 in myocardial fibrosis induced by diabetes in mice. We used normal C57BL/6 wild type (WT) and miR-155 knockout (KO) mice to establish the diabetic model by intraperitoneal injection of streptozotocin, and we utilized echocardiography to evaluate the cardiac function at 30 and 60 days post-modeling. Hematoxylin-eosin (HE) and sirius-red (SR) staining were used to evaluate the degree of myocardial lesions. Furthermore, we extracted cardiac fibroblasts (CFs) from the WT mice and transfected them with miR-155 inhibitors, mimics and negative control siRNAs to analyze the specific mechanism involved in the development of myocardial fibrosis. The results showed that miR-155 deficiency could prevent cardiac fibrosis induced by diabetes in mice and also that attenuated collagen synthesis is induced by high glucose (HG) in CFs. We found that miR-155 regulated cardiac fibrosis via the TGF-β1-Smad 2 signaling pathway. These findings suggest that miR-155 may be a therapeutic target for preventing cardiac fibrosis induced by diabetes.
Insights
microRNA-155 (miR-155) deficiency prevents cardiac fibrosis in diabetic mice. This study reveals miR-155 regulates fibrosis through the TGF-β1-Smad2 pathway, suggesting it as a therapeutic target.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Fibrosis Research
Background:
- Cardiac fibrosis is a key pathological process in heart diseases.
- microRNA-155 (miR-155) is implicated in fibrotic diseases, but its role in myocardial fibrosis is unclear.
- Understanding miR-155's mechanism in diabetic cardiomyopathy is crucial.
Purpose of the Study:
- To investigate the biological function of miR-155 in diabetes-induced myocardial fibrosis in mice.
- To elucidate the molecular mechanism by which miR-155 influences cardiac fibrosis.
- To assess miR-155 as a potential therapeutic target for diabetic heart disease.
Main Methods:
- Diabetic mouse models (wild type and miR-155 knockout) were established using streptozotocin.
- Cardiac function was assessed using echocardiography.
- Myocardial fibrosis was evaluated via Hematoxylin-eosin and Sirius-red staining.
- Cardiac fibroblasts were treated with miR-155 inhibitors/mimics to analyze the TGF-β1-Smad2 pathway.
Main Results:
- miR-155 deficiency significantly attenuated cardiac fibrosis in diabetic mice.
- High glucose-induced collagen synthesis in cardiac fibroblasts was reduced by miR-155 inhibition.
- miR-155 was found to regulate cardiac fibrosis via the TGF-β1-Smad2 signaling pathway.
Conclusions:
- miR-155 plays a critical role in promoting cardiac fibrosis in the context of diabetes.
- Targeting miR-155 may offer a novel therapeutic strategy for preventing diabetic cardiomyopathy.
- The TGF-β1-Smad2 pathway is a key mediator of miR-155's effects on cardiac fibrosis.
