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Angiotensin II increases secreted frizzled-related protein 5 (sFRP5) expression through AT1 receptor/Rho/ROCK1/JNK signaling in cardiomyocytes

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Abstract

Secreted frizzled-related protein 5 (sFRP5) is a novel adipokine that functions as an inhibitor of Wnt signaling and is involved in embryonic development, proliferation, atherosclerosis, and apoptosis. Studies have shown that sFRP1-4 is expressed in cardiomyocytes, and sFRP3 and sFRP4 are elevated during heart failure. However, it is unclear whether sFRP5 is expressed in cardiomyocytes or cardiac hypertrophy, and as regards the effects of sFRP5 in the process. Here, we report the expression and the corresponding mechanisms of sFRP5 in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. Neonatal rat ventricular myocytes were exposed to increasing concentrations of Ang II for 12–72 h. Y27632 was used to block ROCK signal. PD98059, SB203580, and SP600125 were used to inhibit ERK1/2, p38 MAPK, and JNK signaling pathways, respectively, and anisomycin was used to activate JNK pathway. RT-PCR and Western-blot determined the expressions of sFRP5. BNP, TNF-α, ROCK1, ROCK2, MYPT1, and JNK were examined through Western-blot analysis. Ang II increased sFRP5 mRNA and protein levels in a time- and dose-dependent manner. Telmisartan, Y27632 and SP600125 effectively suppressed the expression of sFRP5. sFRP5 downregulated BNP and TNF-α expressions in hypertrophic cardiomyocytes. sFRP5 is expressed in cardiomyocytes, and upregulated in Ang II-induced cardiomyocyte hypertrophy through the AT1 receptor/Rho/ROCK1/JNK signaling pathway. sFRP5 may play an important role during cardiomyocyte hypertrophy.

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Acknowledgments

This work was supported by Grants from The Nature Science Foundation of Hebei Province (Grant No. H2014206389).

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China

    Xin Jin, Bingyan Guo, Jie Yan, Rong Yang, Liang Chang, Yaling Wang, Chenglong Miao, Suyun Liu, Hui Zhang & Yongjun Li

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  1. Xin Jin
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  2. Bingyan Guo
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  3. Jie Yan
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Correspondence to Yongjun Li.

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Jin, X., Guo, B., Yan, J. et al. Angiotensin II increases secreted frizzled-related protein 5 (sFRP5) expression through AT1 receptor/Rho/ROCK1/JNK signaling in cardiomyocytes. Mol Cell Biochem 408, 215–222 (2015). https://doi.org/10.1007/s11010-015-2497-9

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  • DOI: https://doi.org/10.1007/s11010-015-2497-9

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