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Fibroblast growth factor 21 protects rat cardiomyocytes from endoplasmic reticulum stress by promoting the fibroblast growth factor receptor 1-extracellular signal‑regulated kinase 1/2 signaling pathway

  • Authors:
    • Pingping Liang
    • Lin Zhong
    • Lei Gong
    • Jiahui Wang
    • Yujie Zhu
    • Weifeng Liu
    • Jun Yang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Yantai Yuhuangding Hospital, Affiliated Hospital of Medical College Qingdao University, Yantai, Shandong 264000, P.R. China, Biochip Laboratory, Yantai Yuhuangding Hospital, Affiliated Hospital of Medical College Qingdao University, Yantai, Shandong 264000, P.R. China, Central Laboratory, Yantai Yuhuangding Hospital, Affiliated Hospital of Medical College Qingdao University, Yantai, Shandong 264000, P.R. China
    Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1477-1485
    |
    Published online on: September 19, 2017
       https://doi.org/10.3892/ijmm.2017.3140
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Abstract

Fibroblast growth factor 21 (FGF21), as an endocrine factor, is secreted into circulation by injured cardiomyocytes. Endoplasmic reticulum (ER) stress-induced apoptosis has been proposed as an important pathophysiological mechanism for cardiomyocyte injury. However, whether the enhanced expression of FGF21 in cardiomyocytes is linked to ER stress, and the effect and underlying mechanism of FGF21 on ER stress-induced cardiomyocyte apoptosis remain unclear. In the present study, it was demonstrated that mild ER stress resulted in upregulated expression levels of FGF21 and its main receptors, as a response to cell compensation, at the induction of ≤5 µM tunicamycin (TM). However, excessive ER stress (TM ≥10 µM) activated the ER stress-mediated apoptosis signaling pathways, including PKR-like ER kinase (PERK)-eukaryotic translational initiation factor 2α (eIF2α)-activating transcription factor 4 (ATF4)-CCAAT/-enhancer-binding protein homologous protein (CHOP) and inositol-requiring kinase 1α (IRE1α)-c-Jun N-terminal kinases (JNK), as well as inhibited the expression of FGF21 and its primary receptors. In addition, FGF21 overexpression provided protection against ER stress-induced cardiomyocyte injury, as evidenced by increased cell viability and reduced apoptosis. These changes were associated with the inhibition of ER stress-mediated apoptosis signaling pathways, as well as increased phosphorylation of FGFR1 and ERK1/2. However, the protective effects of overexpressed FGF21 were abolished following treatment with FGFR1 and ERK1/2 inhibitors. Thus, mild ER stress may induce the expression of FGF21 and its primary receptors in cardiomyocytes. FGF21 inhibits ER stress-induced cardiomyocyte injury as least in part via the FGFR1-ERK1/2 signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Liang P, Zhong L, Gong L, Wang J, Zhu Y, Liu W and Yang J: Fibroblast growth factor 21 protects rat cardiomyocytes from endoplasmic reticulum stress by promoting the fibroblast growth factor receptor 1-extracellular signal‑regulated kinase 1/2 signaling pathway. Int J Mol Med 40: 1477-1485, 2017.
APA
Liang, P., Zhong, L., Gong, L., Wang, J., Zhu, Y., Liu, W., & Yang, J. (2017). Fibroblast growth factor 21 protects rat cardiomyocytes from endoplasmic reticulum stress by promoting the fibroblast growth factor receptor 1-extracellular signal‑regulated kinase 1/2 signaling pathway. International Journal of Molecular Medicine, 40, 1477-1485. https://doi.org/10.3892/ijmm.2017.3140
MLA
Liang, P., Zhong, L., Gong, L., Wang, J., Zhu, Y., Liu, W., Yang, J."Fibroblast growth factor 21 protects rat cardiomyocytes from endoplasmic reticulum stress by promoting the fibroblast growth factor receptor 1-extracellular signal‑regulated kinase 1/2 signaling pathway". International Journal of Molecular Medicine 40.5 (2017): 1477-1485.
Chicago
Liang, P., Zhong, L., Gong, L., Wang, J., Zhu, Y., Liu, W., Yang, J."Fibroblast growth factor 21 protects rat cardiomyocytes from endoplasmic reticulum stress by promoting the fibroblast growth factor receptor 1-extracellular signal‑regulated kinase 1/2 signaling pathway". International Journal of Molecular Medicine 40, no. 5 (2017): 1477-1485. https://doi.org/10.3892/ijmm.2017.3140
Copy and paste a formatted citation
x
Spandidos Publications style
Liang P, Zhong L, Gong L, Wang J, Zhu Y, Liu W and Yang J: Fibroblast growth factor 21 protects rat cardiomyocytes from endoplasmic reticulum stress by promoting the fibroblast growth factor receptor 1-extracellular signal‑regulated kinase 1/2 signaling pathway. Int J Mol Med 40: 1477-1485, 2017.
APA
Liang, P., Zhong, L., Gong, L., Wang, J., Zhu, Y., Liu, W., & Yang, J. (2017). Fibroblast growth factor 21 protects rat cardiomyocytes from endoplasmic reticulum stress by promoting the fibroblast growth factor receptor 1-extracellular signal‑regulated kinase 1/2 signaling pathway. International Journal of Molecular Medicine, 40, 1477-1485. https://doi.org/10.3892/ijmm.2017.3140
MLA
Liang, P., Zhong, L., Gong, L., Wang, J., Zhu, Y., Liu, W., Yang, J."Fibroblast growth factor 21 protects rat cardiomyocytes from endoplasmic reticulum stress by promoting the fibroblast growth factor receptor 1-extracellular signal‑regulated kinase 1/2 signaling pathway". International Journal of Molecular Medicine 40.5 (2017): 1477-1485.
Chicago
Liang, P., Zhong, L., Gong, L., Wang, J., Zhu, Y., Liu, W., Yang, J."Fibroblast growth factor 21 protects rat cardiomyocytes from endoplasmic reticulum stress by promoting the fibroblast growth factor receptor 1-extracellular signal‑regulated kinase 1/2 signaling pathway". International Journal of Molecular Medicine 40, no. 5 (2017): 1477-1485. https://doi.org/10.3892/ijmm.2017.3140
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