title: miR-155 regulates high glucose-induced cardiac fibrosis via the TGF-β signaling pathway.
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.
authors.affiliation: Chinese 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.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Chinese 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.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Chinese 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Chinese 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.
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Luo
authors.affiliation: Chinese 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.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Chinese 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.
authors.forename: Yue
authors.identifier: http://orcid.org/0000-0002-1775-9174
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D005355:Fibrosis; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D005947:Glucose / Q000378:metabolism*; D006334:Heart Function Tests; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D058628:Myofibroblasts / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016212:Transforming Growth Factor beta; D003094:Collagen; D005947:Glucose