Overexpression of cardiac-specific IGF-IIRα accelerates the development of liver dysfunction through STZ-induced diabetic hepatocyte damage in transgenic rats

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Title:	Overexpression of cardiac-specific IGF-IIRα accelerates the development of liver dysfunction through STZ-induced diabetic hepatocyte damage in transgenic rats
Authors:	Li, Chi-Cheng;Li, Chi-Cheng;Rame, Samiraj;Ramesh, Samiraj;Liu, Tzu-Yang;Liu, Tzu-Yang;Wang, Tso-Fu;Wang, Tso-Fu;Kuo, Wei-Wen;Kuo, Wei-Wen;Kuo, Chia-Hua;Kuo, Chia-Hua;Ch, Yung-Ming;Chang, Yung-Ming;Dennis, Jine-;Hsieh, Dennis Jine-Yuan;Ming-Cheng, Cheng C;Chen, Ming-Cheng;黃志揚;Huang, Chih-Yang
Contributors:	醫學暨健康學院醫學檢驗暨生物技術學系
Keywords:	IGF-IIRα;cardio-hepatic syndrome;hepatocyte damage;liver dysfunction;transgenic rats.
Date:	2022-08-01
Issue Date:	2023-03-29 02:23:31 (UTC+0)
Publisher:	亞洲大學
Abstract:	This study reports the effect of cardiac-specific insulin-like growth factor-II receptor α (IGF-IIRα) overexpression on the development of liver dysfunction in transgenic rats via STZ-induced diabetic hepatocyte damage. The cardio-hepatic syndrome comprises a number of heart and liver illnesses in which an acute or chronic disease in one organ can lead to acute or chronic disease in the other. However, the molecular mechanism involved in such a set of conditions is unclear. In this study, we developed a transgenic rat model with cardiac-specific overexpression of IGF-IIRα, which is a supplementary splicing variant of insulin-like growth factor-II receptor (IGF-IIR), expressed in pathological hearts, to investigate the relationship between late fetal gene expression in diabetic hearts and their influence on diabetic hepatopathy. STZ (55 mg/kg) was intraperitoneally delivered into IGF-IIR overexpressed transgenic (TG) and non-transgenic (NTG) animal models developed in Sprague-Dawley (SD) rats after an overnight fast. The relationship among IGF-IIRα overexpression and hepatocyte damages have been determined based on the complexity of damage in the liver. Our findings revealed that overexpression of the cardiac-specific IGF-IIRα enhances diabetes-induced morphological alterations and hepatic inflammation in the livers. The diabetic transgenic rats demonstrated the development of pathological conditions such as thick collagen fiber deposition, bridging fibrosis, and elevation of α-SMA and MMP1 related liver fibrosis mechanisms. Our data suggest that IGF-IIRα overexpression in the heart during a pathological state may worsen diabetic hepatopathy in rats.
Appears in Collections:	[生物科技學系] 期刊論文

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