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  • Title: Urocortin attenuates myocardial fibrosis in diabetic rats via the Akt/GSK-3β signaling pathway.
    Author: Liu X, Liu C, Li J, Zhang X, Song F, Xu J.
    Journal: Endocr Res; 2016 May; 41(2):148-57. PubMed ID: 26934363.
    Abstract:
    OBJECTIVE: Urocortin, a novel identified corticotropin-releasing factor-related endocrinal peptide, has been shown to play an essential role in cardioprotection. Until recently, whether urocortin can protect the heart against diabetic cardiomyopathy (DCM) remained unclear. Herein, we evaluated the cardioprotective effect of urocortin on cardiac dysfunction, inflammation, and fibrosis and demonstrated the potential mechanism in a diabetic rat model. METHODS: Diabetic rats were randomly divided into 4 groups: diabetic control group, urocortin, urocortin + astressin (a selective CRF receptor 2 antagonist) and urocortin + triciribine (an Akt pathway blocker). Cardiac catheterization was performed to evaluate cardiac function. The levels of creatine phosphokinase isoenzyme (CK-MB), plasma brain natriuretic peptide (BNP), myocardial collagen volume fraction (CVF) and left ventricular mass index (LVWI) were measured. Inflammatory factors (transforming growth factor beta 1, TGF-β1; connective tissue growth factor, CTGF) and activation of signaling proteins (Akt, GSK-3β) were also detected using western blot. RESULTS: DCM was successfully induced by the injection of streptozotocin (STZ) as evidenced by abnormal heart mass and cardiac function as well as the imbalance of extracellular matrix homeostasis. Rats in the DCM group showed increased mRNA and protein levels of LVWI, BNP, CK-MB, CVF, TGF-β1 and CTGF compared to the control group, which were accompanied with diminished phosphorylation of Akt and GSK-3β. Interestingly, myocardial dysfunction, cardiac fibrosis, and inflammation were suppressed by urocortin in the heart of diabetic rats. Moreover, inhibition of phosphorylation of Akt and GSK-3β was also reversed by urocortin. These effects of urocortin were suppressed by astressin. In addition, triciribine partially reduced the effects of urocortin on myocardial dysfunction, inflammation, and cardiac fibrosis. CONCLUSIONS: These results suggest that urocortin exhibits a therapeutic benefit in the treatment of DCM by attenuating fibrosis and inflammation. Furthermore, inhibition of the Akt/GSK-3β signaling pathway may be partially responsible for these effects.
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