Fibroblast growth factor-21 alleviates hypoxia/reoxygenation injury in H9c2 cardiomyocytes by promoting autophagic flux

Ren,Zhong; Xiao,Weijin; Zeng,Yun; Liu,Mi‑Hua; Li,Guo‑Hua; Tang,Zhi‑Han; Qu,Shun‑Lin; Hao,Ya‑Meng; Yuan,Hou‑Qin; Jiang,Zhi‑Sheng

doi:10.3892/ijmm.2019.4071

Fibroblast growth factor-21 alleviates hypoxia/reoxygenation injury in H9c2 cardiomyocytes by promoting autophagic flux

Authors:
- Zhong Ren
- Weijin Xiao
- Yun Zeng
- Mi‑Hua Liu
- Guo‑Hua Li
- Zhi‑Han Tang
- Shun‑Lin Qu
- Ya‑Meng Hao
- Hou‑Qin Yuan
- Zhi‑Sheng Jiang
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Affiliations: Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang, Hunan 421001, P.R. China, Department of Clinical Laboratory, Nanhua Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
Published online on: January 21, 2019 https://doi.org/10.3892/ijmm.2019.4071
Pages: 1321-1330
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Fibroblast growth factor (FGF)‑21, a member of the family of FGFs, exhibits protective effects against myocardial ischemia and ischemia/reperfusion injury; it is also an enhancer of autophagy. However, the mechanisms underlying the protective role of FGF‑21 against cardiomyocyte hypoxia/reoxygenation (H/R) injury remain unclear. The present study aimed to investigate the effect of FGF‑21 on H9c2 cardiomyocyte injury induced by H/R and the mechanism associated with changes in autophagy. Cultured H9c2 cardiomyocytes subjected to hypoxia were treated with a vehicle or FGF‑21 during reoxygenation. The viability of H9c2 rat cardiomyocytes was measured using Cell Counting Kit‑8 and trypan blue exclusion assays. The contents of creatine kinase (CK) and creatine kinase isoenzymes (CK‑MB), cardiac troponin I (cTnT), cardiac troponin T (cTnI) and lactate dehydrogenase (LDH) in culture medium were detected with a CK, CK‑MB, cTnT, cTnI and LDH assay kits. The protein levels were examined by western blot analysis. Autophagic flux was detected by Ad‑mCherry‑GFP‑LC3B autophagy fluorescent adenovirus reagent. The results indicated that FGF‑21 alleviated H/R‑induced H9c2 myocardial cell injury and enhanced autophagic flux during H/R, and that this effect was antagonized by co‑treatment with 3‑methyladenine, an autophagy inhibitor. Furthermore, FGF‑21 increased the expression levels of Beclin‑1 and Vps34 proteins, but not of mechanistic target of rapamycin. These data indicate that FGF‑21 treatment limited H/R injury in H9c2 cardiomyocytes by promoting autophagic flux through upregulation of the expression levels of Beclin‑1 and Vps34 proteins.

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