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Urocortin attenuates myocardial fibrosis in diabetic rats via the Akt/GSK-3β signaling pathway.
Endocr Res. 2016 May; 41(2):148-57.ER

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.

Authors+Show Affiliations

a The First Affiliated Hospital of Liaoning Medical University , Jinzhou , China. b Department of Endocrinology , Provincial Hospital Affiliated to Shandong University , Jinan , China.c Department of Pharmacology , Liaoning Medical University , Jinzhou , China.a The First Affiliated Hospital of Liaoning Medical University , Jinzhou , China.a The First Affiliated Hospital of Liaoning Medical University , Jinzhou , China.a The First Affiliated Hospital of Liaoning Medical University , Jinzhou , China.b Department of Endocrinology , Provincial Hospital Affiliated to Shandong University , Jinan , China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26934363

Citation

Liu, Xinyu, et al. "Urocortin Attenuates Myocardial Fibrosis in Diabetic Rats Via the Akt/GSK-3β Signaling Pathway." Endocrine Research, vol. 41, no. 2, 2016, pp. 148-57.
Liu X, Liu C, Li J, et al. Urocortin attenuates myocardial fibrosis in diabetic rats via the Akt/GSK-3β signaling pathway. Endocr Res. 2016;41(2):148-57.
Liu, X., Liu, C., Li, J., Zhang, X., Song, F., & Xu, J. (2016). Urocortin attenuates myocardial fibrosis in diabetic rats via the Akt/GSK-3β signaling pathway. Endocrine Research, 41(2), 148-57. https://doi.org/10.3109/07435800.2015.1094489
Liu X, et al. Urocortin Attenuates Myocardial Fibrosis in Diabetic Rats Via the Akt/GSK-3β Signaling Pathway. Endocr Res. 2016;41(2):148-57. PubMed PMID: 26934363.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Urocortin attenuates myocardial fibrosis in diabetic rats via the Akt/GSK-3β signaling pathway. AU - Liu,Xinyu, AU - Liu,Chunna, AU - Li,Jian, AU - Zhang,Xiaoyan, AU - Song,Feiran, AU - Xu,Jin, Y1 - 2016/03/02/ PY - 2016/3/3/entrez PY - 2016/3/5/pubmed PY - 2017/2/28/medline KW - Myocardial fibrosis KW - corticotrophine releasing hormone KW - dilatetes KW - mellitus KW - transforming growth factor beta 1 KW - urocortin SP - 148 EP - 57 JF - Endocrine research JO - Endocr. Res. VL - 41 IS - 2 N2 - 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. SN - 1532-4206 UR - https://www.unboundmedicine.com/medline/citation/26934363/Urocortin_attenuates_myocardial_fibrosis_in_diabetic_rats_via_the_Akt/GSK_3β_signaling_pathway_ L2 - http://www.tandfonline.com/doi/full/10.3109/07435800.2015.1094489 DB - PRIME DP - Unbound Medicine ER -