Lin28a protects against diabetic cardiomyopathy via the PKA/ROCK2 pathway

Shuhong Sun, Mingming Zhang, Jie Lin, Jianqiang Hu, Rongqing Zhang, Congye Li, Tianlu Wei, Dongdong Sun, Jianqin Wei, Haichang Wang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)29-36
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume469
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • Apoptosis
  • Autophagy
  • Diabetic cardiomyopathy DCM
  • Lin28a

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Lin28a protects against diabetic cardiomyopathy via the PKA/ROCK2 pathway'. Together they form a unique fingerprint.

Cite this