title: Role of miR-24, Furin, and Transforming Growth Factor-β1 Signal Pathway in Fibrosis After Cardiac Infarction.
abstract: BACKGROUND Cardiac fibrosis after primary infarction is a type of pathological phenomena as shown by increased collagen in myocardial cells. Transforming growth factor (TGF)-β1 is a critical factor participating in myocardial fibrosis. A previous study has shown the inhibitory role on TGF-β1 by microRNA-24 (miR-24) via targeting Furin. This study thus investigated the role of miR-24 and Furin/TGF-β1 in rat myocardial fibrosis. MATERIAL AND METHODS A total of 40 adult SD rats (both males and females) were prepared for myocardial infarction model by ligating the descending branch of left coronary artery after anesthesia. HE staining was performed to observe myocardial fibrosis after 1, 2, and 4 weeks. Tissue RNA was extracted to detect mRNA levels of Furin, TGF-β1, and miR-24 by real-time PCR. Western blotting was used to quantify protein expression of Furin and TGF-β1 in myocardial tissues. RESULTS Increased connective tissues were observed in myocardial tissues at 4 weeks after infarction by HE staining, which also revealed widening of the intra-myocardial cleft, along with more inflammatory cells and fibroblast hypertrophy. miR-24 expression was significantly depressed at 2 and 4 weeks after cardiac infarction (p<0.05). mRNA levels of Furin and TGF-β1 were elevated after infarction (p<0.05). With prolonged time periods of myocardial infarction, protein levels of Furin and TGF-β1 were further increased. The level of miR-24 was positively correlated with left ventricular end-diastolic diameter, left ventricular systolic diameter, and left ventricular ejection fraction. However, the level of Furin or TGF-β1 was negatively correlated with the above parameters. CONCLUSIONS This study demonstrated the important role of abnormal expression of miR-24 in myocardial fibrosis after infarction, and may provide drug targets for treating myocardial fibrosis.
authors.affiliation: Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Zhufeng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Sumei
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Miao
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Rui
authors.initials: R
authors.lastname: Ren
authors.affiliation: Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Wanshan
authors.initials: W
authors.lastname: Ma
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045683:Furin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D015291:Transforming Growth Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C574736:MIRN24 microRNA, rat; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1; D015291:Transforming Growth Factors; D045683:Furin