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Calcium‑sensing receptor promotes high glucose‑induced myocardial fibrosis via upregulation of the TGF‑β1/Smads pathway in cardiac fibroblasts

  • Authors:
    • Hui Yuan
    • Yuqi Fan
    • Yuehong Wang
    • Tielei Gao
    • Yiying Shao
    • Bingbing Zhao
    • Hongzhu Li
    • Changqing Xu
    • Can Wei
  • View Affiliations / Copyright

    Affiliations: Department of Pathophysiology, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
    Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1093-1102
    |
    Published online on: June 4, 2019
       https://doi.org/10.3892/mmr.2019.10330
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Abstract

Diabetic cardiomyopathy (DCM) is a major complication of diabetes and myocardial fibrosis is its major pathological feature. Calcium‑sensing receptor (CaSR) is a G protein‑coupled receptor and participates in the regulation of calcium homeostasis; it is implicated in a range of diseases, including myocardial ischemia/reperfusion injury, myocardial infarction and pulmonary hypertension. However, whether CaSR is associated with myocardial fibrosis in DCM has remained elusive. In the present study, type 1 diabetic (T1D) rats and primary neonatal rat cardiac fibroblasts (CFs) were used to observe changes in CaSR to assess its potential as an indicator of myocardial fibrosis. The in vivo experiments revealed that in the T1D and CaSR agonist (R568) groups, evident collagen (Col)‑I and ‑III deposition was present after 12 weeks. Furthermore, the in vitro experiment indicated that the levels of transforming growth factor (TGF)‑β1, phosphorylated (p‑) protein kinase C, p‑p38, p‑Smad2, TβRI, TβRII, along with the intracellular Ca2+ levels and the content of TGF‑β1 in the culture medium were significantly increased in a high‑glucose (HG) group and an R568‑treated group. Treatment with the CaSR inhibitor Calhex231 significantly inhibited the abovementioned changes. Collectively, the results indicated that the increase of CaSR expression in CFs may induce intracellular Ca2+ increases and the activation of TGF‑β1/Smads, and enhance the proliferation of CFs, along with the excessive deposition of Col, resulting in myocardial fibrosis. The present results indicate an important novel mechanism for HG‑induced myocardial fibrosis and suggest that CaSR may be a promising potential therapeutic target for DCM.
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Copy and paste a formatted citation
Spandidos Publications style
Yuan H, Fan Y, Wang Y, Gao T, Shao Y, Zhao B, Li H, Xu C and Wei C: Calcium‑sensing receptor promotes high glucose‑induced myocardial fibrosis via upregulation of the TGF‑β1/Smads pathway in cardiac fibroblasts. Mol Med Rep 20: 1093-1102, 2019.
APA
Yuan, H., Fan, Y., Wang, Y., Gao, T., Shao, Y., Zhao, B. ... Wei, C. (2019). Calcium‑sensing receptor promotes high glucose‑induced myocardial fibrosis via upregulation of the TGF‑β1/Smads pathway in cardiac fibroblasts. Molecular Medicine Reports, 20, 1093-1102. https://doi.org/10.3892/mmr.2019.10330
MLA
Yuan, H., Fan, Y., Wang, Y., Gao, T., Shao, Y., Zhao, B., Li, H., Xu, C., Wei, C."Calcium‑sensing receptor promotes high glucose‑induced myocardial fibrosis via upregulation of the TGF‑β1/Smads pathway in cardiac fibroblasts". Molecular Medicine Reports 20.2 (2019): 1093-1102.
Chicago
Yuan, H., Fan, Y., Wang, Y., Gao, T., Shao, Y., Zhao, B., Li, H., Xu, C., Wei, C."Calcium‑sensing receptor promotes high glucose‑induced myocardial fibrosis via upregulation of the TGF‑β1/Smads pathway in cardiac fibroblasts". Molecular Medicine Reports 20, no. 2 (2019): 1093-1102. https://doi.org/10.3892/mmr.2019.10330
Copy and paste a formatted citation
x
Spandidos Publications style
Yuan H, Fan Y, Wang Y, Gao T, Shao Y, Zhao B, Li H, Xu C and Wei C: Calcium‑sensing receptor promotes high glucose‑induced myocardial fibrosis via upregulation of the TGF‑β1/Smads pathway in cardiac fibroblasts. Mol Med Rep 20: 1093-1102, 2019.
APA
Yuan, H., Fan, Y., Wang, Y., Gao, T., Shao, Y., Zhao, B. ... Wei, C. (2019). Calcium‑sensing receptor promotes high glucose‑induced myocardial fibrosis via upregulation of the TGF‑β1/Smads pathway in cardiac fibroblasts. Molecular Medicine Reports, 20, 1093-1102. https://doi.org/10.3892/mmr.2019.10330
MLA
Yuan, H., Fan, Y., Wang, Y., Gao, T., Shao, Y., Zhao, B., Li, H., Xu, C., Wei, C."Calcium‑sensing receptor promotes high glucose‑induced myocardial fibrosis via upregulation of the TGF‑β1/Smads pathway in cardiac fibroblasts". Molecular Medicine Reports 20.2 (2019): 1093-1102.
Chicago
Yuan, H., Fan, Y., Wang, Y., Gao, T., Shao, Y., Zhao, B., Li, H., Xu, C., Wei, C."Calcium‑sensing receptor promotes high glucose‑induced myocardial fibrosis via upregulation of the TGF‑β1/Smads pathway in cardiac fibroblasts". Molecular Medicine Reports 20, no. 2 (2019): 1093-1102. https://doi.org/10.3892/mmr.2019.10330
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