Browsing by Author "Singh, Gurinder B."

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    miR-30c and miR-181a synergistically modulate p53?p21 pathway in diabetes induced cardiac hypertrophy
    (Springer New York LLC, 2016) Raut, Satish K.; Singh, Gurinder B.; Rastogi, Bhawna; Saikia, Uma Nahar; Mittal, Anupam; Dogra, Nilambra; Singh, Sandeep; Prasad, Rishikesh; Khullar, Madhu
    p53?p21 pathway mediates cardiomyocyte hypertrophy and apoptosis and is upregulated in diabetic cardiomyopathy (DbCM). We investigated role of microRNAs in regulating p53?p21 pathway in high glucose (HG)-induced cardiomyocyte hypertrophy and apoptosis. miR-30c and miR-181a were identified to target p53. Cardiac expression of microRNAs was measured in diabetic patients, diabetic rats, and in HG-treated cardiomyocytes. Effect of microRNAs over-expression and inhibition on HG-induced cardiomyocyte hypertrophy and apoptosis was examined. Myocardial expression of p53 and p21 genes was increased and expression of miR-30c and miR-181a was significantly decreased in diabetic patients, DbCM rats, and in HG-treated cardiomyocytes. Luciferase assay confirmed p53 as target of miR-30c and miR-181a. Over-expression of miR-30c or miR-181a decreased expression of p53, p21, ANP, cardiomyocyte cell size, and apoptosis in HG-treated cardiomyocytes. Concurrent over-expression of these microRNAs resulted in greater decrease in cardiomyocyte hypertrophy and apoptosis, suggesting a synergistic effect of these microRNAs. Our results suggest that dysregulation of miR-30c and miR-181a may be involved in upregulation of p53?p21 pathway in DbCM. ? 2016, Springer Science+Business Media New York.