Islet transplantation attenuates cardiac fibrosis in diabetic rats through inhibition of TGF-β1/Smad3 pathway

American Journal of Translational Research

Hong-Wei Wang¹  Yi-He Chen²  Xian-Dong Zhu³  Wei Huang⁴  Yan-Yan Chen⁵  Fu-Biao Ni⁶ 

[1] Department of Cardiology, The First Afliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou 325000, Zhejiang, China;Department of Hepatobiliary and Pancreatic Surgery Laboratory, The First Afliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou 325000, Zhejiang, China;Department of Neurology, The First Afliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou 325000, Zhejiang, China;Department of Nutrition, The First Afliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou 325000, Zhejiang, China;Department of Transplantation, The First Afliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou 325000, Zhejiang, China;School of Pharmacy, Wenzhou Medical University, Nanbaixiang, Wenzhou 325000, Zhejiang, China

关键词: Diabetes mellitus;    islet transplantation;    cardiac fibrosis;    TGF-β;    1/Smad3 signaling;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Although islet transplantation has been identified as a promising endocrine replacement treatment for patient with diabetes mellitus (DM), it still remains unclear whether islet transplantation can inhibit the diabetic-induced myocardial injury and subsequent adverse ventricular remodeling. Here, we sought to explore the molecular mechanism underlying the cardioprotective effect of islet transplantation. We established the diabetic rat model by intraperitoneal injection of STZ, which was followed by either islet transplantation or conventional insulin treatment. Compared with insulin treatment, islet transplantation further reduced the elevated blood glucose which was nearly restored to normoglycaemia. In addition, islet transplantation attenuated the increased levels of cTn-I and CK-MB, cleaved-caspase-3 in response to DM, and ameliorated diabetic-induced cardiac hypertrophy and interstitial fibrosis, along with improved extracellular matrix (ECM) deposition. Moreover, diabetic rats that underwent islet transplantation had lower expression of TGF-β1 and lower phosphorylation levels of Smad3. Therefore, islet transplantation exerted protective effect against diabetic-induced myocardial injury and fibrotic remodeling through deactivation of TGF-β1/Smad3 signaling pathway.

【 授权许可】

CC BY-NC