title: miR-30c Mediates Upregulation of Cdc42 and Pak1 in Diabetic Cardiomyopathy.
abstract: OBJECTIVE
  Cardiac hypertrophy and myocardial fibrosis significantly contribute to the pathogenesis of diabetic cardiomyopathy (DCM). Altered expression of several genes and their regulation by microRNAs has been reported in hypertrophied failing hearts. This study aims to examine the role of Cdc42, Pak1, and miR-30c in the pathogenesis of cardiac hypertrophy in DCM.
  
  
  METHODS
  DCM was induced in Wistar rats by low-dose streptozotocin-high-fat diet for 12 weeks. Cardiac expression of Cdc42, Pak1 and miR-30c, and hypertrophy markers (ANP and β-MHC) was studied in DCM vs control rats and in high-glucose (HG)-treated H9c2 cardiomyocytes.
  
  
  RESULTS
  Diabetic rats showed cardiomyocyte hypertrophy, increased heart-to-body weight ratio, and an increased expression of ANP and β-MHC. Cardiac expression of Cdc42 and Pak1 genes was increased in diabetic hearts and in HG-treated cardiomyocytes. miR-30c was identified to target Cdc42 and Pak1 genes, and cardiac miR-30c expression was found to be decreased in DCM rats, patients with DCM, and in HG-treated cardiomyocytes. miR-30c overexpression decreased Cdc42 and Pak1 genes and attenuated HG-induced cardiomyocyte hypertrophy, whereas miR-30c inhibition increased Cdc42 and Pak1 gene expression and myocyte hypertrophy in HG-treated cardiomyocytes.
  
  
  CONCLUSIONS
  Downregulation of miR-30c mediates prohypertrophic effects of hyperglycemia in DCM by upregulation of Cdc42 and Pak1 genes.
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 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, 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, India.
authors.forename: Gurinder B
authors.initials: GB
authors.lastname: Singh
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Uma
authors.initials: U
authors.lastname: Nahar
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Vibhuti
authors.initials: V
authors.lastname: Sharma
authors.affiliation: Department of Cardiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Anupam
authors.initials: A
authors.lastname: Mittal
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Madhu
authors.initials: M
authors.lastname: Khullar
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D024722:Cardiac Myosins / Q000378:metabolism; D006332:Cardiomegaly / Q000473:pathology*; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental; D058065:Diabetic Cardiomyopathies / Q000473:pathology*; D035683:MicroRNAs / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D015854:Up-Regulation; D020764:cdc42 GTP-Binding Protein / Q000096:biosynthesis*; D054462:p21-Activated Kinases / Q000096:biosynthesis*
chemical_list: C546086:MIRN30b microRNA, human; C501641:MYH7 protein, human; D035683:MicroRNAs; D013311:Streptozocin; D009320:Atrial Natriuretic Factor; C515903:PAK1 protein, human; D054462:p21-Activated Kinases; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains; D020764:cdc42 GTP-Binding Protein
keywords: Cardiac hypertrophy; Cdc42; Diabetic cardiomyopathy; Pak1; miR-30c