title: Intermedin 1-53 Inhibits Myocardial Fibrosis in Rats by Down-Regulating Transforming Growth Factor-β.
abstract: BACKGROUND Myocardial fibrosis is the result of persistent anoxia and ischemic myocardial fibers caused by coronary atherosclerotic stenosis, which lead to heart failure, threatening the patient's life. This study aimed to explore the regulatory role of intermedin 1-53 (IMD1-53) in cardiac fibrosis using neonatal rat cardiac fibroblasts and a myocardial infarction (MI) rat model both in vitro and in vivo. MATERIAL AND METHODS The Western blot method was used to detect the protein expression of collagen I and collagen III in myocardial fibroblasts. The SYBR Green I real-time quantitative polymerase chain reaction (PCR) assay was used to detect the mRNA expression of collagen type I and III, IMD1-53 calcitonin receptor-like receptor (CRLR), transforming growth factor-β (TGF-β), and matrix metalloproteinase-2 (MMP-2). Masson staining was used to detect the area changes of myocardial fibrosis in MI rats. RESULTS Results in vivo showed that IMD1-53 reduced the scar area on the heart of MI rats and inhibited the expression of collagen type I and III both in mRNA and protein. Results of an in vitro study showed that IMD1-53 inhibited the transformation of cardiomyocytes into myofibroblasts caused by angiotensin II (Ang II). The further mechanism study showed that IMD1-53 inhibited the expression of TGF-β and the phosphorylation of smad3, which further up-regulated the expression of MMP-2. CONCLUSIONS IMD1-53 is an effective anti-fibrosis hormone that inhibits cardiac fibrosis formation after MI by down-regulating the expression of TGF-β and the phosphorylation of smad3, blocking fibrous signal pathways, and up-regulating the expression of MMP-2, thereby demonstrating its role in regression of myocardial fibrosis.
authors.affiliation: Department of Nephrology, Wuhan Medical.
authors.forename: Jian
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Nephrology, Wuhan Medical.
authors.forename: Jiangwei
authors.initials: J
authors.lastname: Luan
authors.affiliation: Department of Nephrology, Wuhan Medical.
authors.forename: Gaohong
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Nephrology, Wuhan Medical.
authors.forename: Chang
authors.initials: C
authors.lastname: Qi
authors.affiliation: Department of Nephrology, Wuhan Medical.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Nephrology, Wuhan Medical.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, Wuhan Medical.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Nephrology, Wuhan Medical.
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Wuhan Medical.
authors.forename: Naipeng
authors.initials: N
authors.lastname: Guo
authors.affiliation: Department of Nephrology, Wuhan Medical.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Internal Medicine-Cardiovascular, Wuhan Medical.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis; D006333:Heart Failure / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: C499411:Adm2 protein, rat; D009479:Neuropeptides; D053773:Transforming Growth Factor beta1; D053607:Adrenomedullin; D003094:Collagen