title: MicroRNA-200c modulates DUSP-1 expression in diabetes-induced cardiac hypertrophy.
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.
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Gurinder Bir
authors.initials: GB
authors.lastname: Singh
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Satish K
authors.initials: SK
authors.lastname: Raut
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Sanskriti
authors.initials: S
authors.lastname: Khanna
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: Rishikesh
authors.initials: R
authors.lastname: Prasad
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. madhu.khullar@gmail.com.
authors.forename: Madhu
authors.initials: M
authors.lastname: Khullar
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000378:metabolism* / Q000473:pathology; D054638:Dual Specificity Phosphatase 1 / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000494:pharmacology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: C555600:MIRN200 microRNA, rat; D035683:MicroRNAs; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D005947:Glucose
keywords: Cardiac hypertrophy; DUSP-1; Diabetic cardiomyopathy; MKP-1; miR-200c