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MicroRNA-200c modulates DUSP-1 expression in diabetes-induced cardiac hypertrophy

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Abstract

Mitogen-activated protein kinases (MAPKs) (ERK1/2, JNK, and p38) are upregulated in diabetic cardiomyopathy (DCM). Dual-specific phosphatase-1 (DUSP-1) has been reported to regulate the activity of MAPKs in cardiac hypertrophy; however, the role of DUSP-1 in regulating MAPKs activity in DCM is not known. MicroRNAs have been reported to regulate the expression of several genes in hypertrophied failing hearts. However, little is known about the microRNAs regulating DUSP-1 expression in diabetes-related cardiac hypertrophy. In the present study, we investigated the role of DUSP-1 and miR-200c in diabetes-induced cardiac hypertrophy. DCM was induced in Wistar rats by low-dose Streptozotocin high-fat diet for 12 weeks. Cardiac expression of ERK, p-38, JNK, DUSP-1, miR-200c, and hypertrophy markers (ANP and β-MHC) was studied in DCM in control rats and in high-glucose (HG)-treated rat neonatal cardiomyocytes. miR-200c inhibition was performed to validate DUSP-1 as target. A significant increase in phosphorylated ERK, p38, and JNK was observed in DCM model and in HG-treated cardiomyocytes (p < 0.05). Expression of DUSP-1 was significantly decreased in diabetes group and in HG-treated cardiomyocytes (p < 0.05). Increased expression of miR-200c was observed in DCM model and in HG-treated cardiomyocytes (p < 0.05). Inhibition of miR-200c induces the expression of the DUSP-1 causing decreased expression of phosphorylated ERK, p38, and JNK and attenuated cardiomyocyte hypertrophy in HG-treated cardiomyocytes. miR-200c plays a role in diabetes-associated cardiac hypertrophy by modulating expression of DUSP-1.

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Acknowledgments

Gurinder Bir Singh is a PhD student in Department of Experimental Medicine and Biotechnology, PGIMER, and fellowship was provided by Department of Biotechnology (DBT-JRF/09-10/295), New Delhi, India.

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Authors and Affiliations

  1. Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Gurinder Bir Singh, Satish K. Raut, Sanskriti Khanna, Akhilesh Kumar, Saurabh Sharma, Rishikesh Prasad & Madhu Khullar

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  1. Gurinder Bir Singh
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  2. Satish K. Raut
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Correspondence to Madhu Khullar.

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Singh, G.B., Raut, S.K., Khanna, S. et al. MicroRNA-200c modulates DUSP-1 expression in diabetes-induced cardiac hypertrophy. Mol Cell Biochem 424, 1–11 (2017). https://doi.org/10.1007/s11010-016-2838-3

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  • DOI: https://doi.org/10.1007/s11010-016-2838-3

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