title: Lin28a protects against diabetic cardiomyopathy via the PKA/ROCK2 pathway.
abstract: BACKGROUND
  Lin28a enhances glucose uptake and insulin-sensitivity. However, the role of Lin28a on experimental diabetic cardiomyopathy (DCM) is not well understood. We investigated the potential role and mechanism ofLin28a in diabetes-induced myocardial dysfunction in mice.
  
  
  METHODS
  Diabetes was induced by intraperitoneal (i.p.) injections of Streptozocin (STZ) in mice. Animals were randomized to be treated with lentivirus carrying Lin28a siRNA or Lin28a cDNA. Cardiac function, cardiomyocyte autophagy, apoptosis and mitochondria morphology in diabetic mice were compared between groups. The target proteins of Lin28a were examined by western blot analysis.
  
  
  RESULTS
  Lin28a levels were markedly reduced in the cardiac tissue compared to the control mice. Lin28a overexpression significantly improved left ventricular ejection fraction (LVEF), promoted autophagy, decreased myocardial apoptotic index and alleviated mitochondria cristae destruction in diabetic mice. Lin28a knockdown exacerbated diabetic injury as evidenced by decreased LVEF, increased apoptotic index and aggravated mitochondria cristae destruction. Interestingly, pretreatment with a PKA inhibitor, N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide], di-HCl Salt (H89) abolished the beneficial effects of Lin28a overexpression. RhoA-expression and ROCK2-expression were decreased in vivo after Lin28a overexpression, while Lin28a knockdown increased the expression of RhoA and ROCK2 in diabetic mice.
  
  
  CONCLUSIONS
  Lin28a protects against DCM through PKA/ROCK2 dependent pathway. Lin28a might serve as a potential therapeutic target for the treatment of the patients with DCM.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Shaanxi Provincial Crops Hospital, Chinese People's Armed Police Forces, Xi' an, 710054, China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Rongqing
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Congye
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Medicine, the First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, China.
authors.forename: Tianlu
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Medicine, Division of Cardiology, Miller's School of Medicine, University of Miami, USA. Electronic address: Jwei@med.miami.edu.
authors.forename: Jianqin
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: wanghc@fmmu.edu.cn.
authors.forename: Haichang
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000150:complications* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015398:Signal Transduction; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000503:physiopathology*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: C488352:Lin-28 protein, mouse; D016601:RNA-Binding Proteins; C515855:Rock2 protein, mouse; D054460:rho-Associated Kinases; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Apoptosis; Autophagy; Diabetic cardiomyopathy DCM; Lin28a