Intermedin 1-53 Inhibits Myocardial Fibrosis in Rats by Down-Regulating Transforming Growth Factor-β
Jian Fang, Jiangwei Luan, Gaohong Zhu, Chang Qi, Zhiyong Yang, Sheng Zhao, Bin Li, Xinzhong Zhang, Naipeng Guo, Xiaodong Li, Dandan Wang
(Department of Nephrology, Wuhan Medical & Healthcare Center for Women and Children, Wuhan Children’s Hospital, Wuhan Women and Children Care Hospital, Wuhan, Hubei, China (mainland))
Med Sci Monit 2017; 23:121-128
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.
Keywords: Fibrosis, Matrix Metalloproteinase 2, Smad3 Protein