title: Protective effects of miR-25 against hypoxia/reoxygenation‑induced fibrosis and apoptosis of H9c2 cells.
abstract: It has been previously demonstrated that microRNA (miR)-25 plays critical roles in collagen deposition. Ischemia/reperfusion injury to the myocardium results in fibrosis and collagen deposition. However, whether miR-25 is involved in the development of hypoxia/reoxygenation (H/R)‑induced fibrosis in cardiomyocytes or not remains largely unknown. For this purpose, in the present study, cardiomyocyte H9c2 cells were subjected to H/R. The techniques of flow cytometry, western blot analysis and RT-qPCR were used and we observed increases in the cell apoptosis rate and fibrosis as well as blocking of the cell cycle in the G1 phase. Moreover, the expression of miR-25 was downregulated after H/R and high‑mobility group box 1 (HMGB1) expression was increased. We also found that the overexpression of miR-25 under conditions of H/R inhibited fibrosis and cell apoptosis as well as reversing the cell cycle blocking. Additionally, the targeting of HMGB1 by miR-25 was confirmed by a dual‑luciferase reporter gene assay. Moreover, the effects of miR-25 were further enhanced by a transforming growth factor-β1 (TGF-β1)/Smad3 inhibitor, SB431542, as fibrosis was reduced and apoptosis was suppressed. In conclusion, the protective effects of miR-25 against H/R-induced fibrosis and apoptosis H9c2 cells were due to direct targeting of HMGB1 through the downregulation of the TGF-β1/Smad3 signaling pathway.
authors: Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, P.R. China.
authors: Qifang
authors: Q
authors: Liu
authors: Department of Cardiology, Heping Hospital, Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China.
authors: Yongjin
authors: Y
authors: Wang
authors: Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, P.R. China.
authors: Tianlun
authors: T
authors: Yang
authors: Department of Cardiology, Heping Hospital, Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China.
authors: Wu
authors: W
authors: Wei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D005355:Fibrosis; D024243:HMGB1 Protein / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010100:Oxygen / Q000494:pharmacology*; D020011:Protective Agents / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; C000598929:MIRN25 microRNA, rat; D035683:MicroRNAs; D020011:Protective Agents; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D010100:Oxygen