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DUSP-1 gene expression is not regulated by promoter methylation in diabetes-associated cardiac hypertrophy
Gurinder Bir Singh1, Sanskriti Khanna1, Satish K Raut1
1Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Background:
The exact mechanism causing decreased expression of the dual specific phosphatase-1 ( DUSP-1) gene in diabetes-associated cardiac hypertrophy is not known. DNA promoter methylation is often associated with decreased gene expression in many diseases including cardiovascular diseases. So, we investigated whether epigenetic silencing via promoter methylation is involved in the decreased expression of DUSP-1 in diabetes-associated cardiac hypertrophy.
Methods:
Real-time polymerase chain reaction (PCR) and Western blotting confirmed the down regulation of the DUSP-1 gene at transcriptional and translational levels. Bisulfite-converted DNA samples from myocardium of rat model of diabetic cardiomyopathy (DCM), high glucose (HG)-treated neonatal rat cardiomyocytes (NRCMs) and cardiac tissues from archived human myocardial DCM autopsies along with their respective controls were analyzed for methylation in the promoter region of the DUSP-1 gene.
Results:
We observed no methylation in the promoter regions of the DUSP-1 gene in DCM rat hearts, in HG-treated NRCMs (between -355 bp and -174 bp) and in cardiac tissues from archived human myocardial DCM autopsies (between -274 bp and -73 bp).
Conclusion:
Methylation-mediated silencing of the DUSP-1 promoter does not appear to be associated with reduced expression, indicating the involvement of other factors in specific suppression of DUSP-1 in diabetes-associated cardiac hypertrophy.