Yan Wu1, Yonghui Liu1, Yitong Pan1, Chunxiao Lu2, Haonan Xu1, Xiaozhi Wang3, Tingting Liu1, Kai Feng1, Yiqun Tang4. 1. Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, Jiangsu, PR China. 2. Department of Geriatric Cardiology, Chinese PLA general hospital, Beijing, 100853, PR China. 3. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 211198, Jiangsu, PR China. 4. Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 211198, Jiangsu, PR China. Electronic address: tyq@cpu.edu.cn.
Abstract
BACKGROUND: Cardiac fibrosis is a crucial factor of heart failure. It has been reported that several microRNAs (miRNAs, miRs) were involved in cardiac fibrosis, however, the role and possible regulatory mechanism of microRNA-135a (miR-135a) in cardiac fibrosis have not been investigated. Here, we explored the regulation mechanism of miR-135a on cardiac fibrosis. METHODS AND RESULTS: In vitro, cardiac fibroblasts (CFs) from neonatal rats were treated by isoproterenol (ISO) at the final concentration of 10 μM for 24 h and miR-135a expression was decreased obviously. A miR-135a mimic inhibited CFs proliferation and differentiation by down-regulating transient receptor potential melastatin 7 (TRPM7) expression and current, whose effects were reversed by either the addition of miR-135a mimic or silencing TRPM7. In vivo, adult SD rat cardiac fibrosis was induced by subcutaneous administration of ISO (5 mg/kg/day) for 10 days. The expression of Collagen I, α-smooth muscle actin (α-SMA) and TRPM7 were up-regulated while miR-135a was down-regulated. In summary, our results illustrated that TRPM7 channel played an essential role in regulating fibrosis and that miR-135a protected against ISO-induced cardiac fibrosis via TRPM7 channel. CONCLUSION: MiR-135a inhibits cardiac fibrosis via miR-135a- TRPM7-collagen production pathway.
BACKGROUND:Cardiac fibrosis is a crucial factor of heart failure. It has been reported that several microRNAs (miRNAs, miRs) were involved in cardiac fibrosis, however, the role and possible regulatory mechanism of microRNA-135a (miR-135a) in cardiac fibrosis have not been investigated. Here, we explored the regulation mechanism of miR-135a on cardiac fibrosis. METHODS AND RESULTS: In vitro, cardiac fibroblasts (CFs) from neonatal rats were treated by isoproterenol (ISO) at the final concentration of 10 μM for 24 h and miR-135a expression was decreased obviously. A miR-135a mimic inhibited CFs proliferation and differentiation by down-regulating transient receptor potential melastatin 7 (TRPM7) expression and current, whose effects were reversed by either the addition of miR-135a mimic or silencing TRPM7. In vivo, adult SD ratcardiac fibrosis was induced by subcutaneous administration of ISO (5 mg/kg/day) for 10 days. The expression of Collagen I, α-smooth muscle actin (α-SMA) and TRPM7 were up-regulated while miR-135a was down-regulated. In summary, our results illustrated that TRPM7 channel played an essential role in regulating fibrosis and that miR-135a protected against ISO-induced cardiac fibrosis via TRPM7 channel. CONCLUSION:MiR-135a inhibits cardiac fibrosis via miR-135a- TRPM7-collagen production pathway.
Authors: Juan E Camacho Londoño; André Marx; Axel E Kraft; Alexander Schürger; Christin Richter; Alexander Dietrich; Peter Lipp; Lutz Birnbaumer; Marc Freichel Journal: Cells Date: 2020-01-29 Impact factor: 6.600
Authors: Mihir Parikh; Branislav Kura; Kimberley A O'Hara; Elena Dibrov; Thomas Netticadan; Jan Slezak; Grant N Pierce Journal: Biomolecules Date: 2020-09-08