Research Paper|Volume 13, Issue 13|pp 17536—17547

IGF IIRα-triggered pathological manifestations in the heart aggravate renal inflammation in STZ-induced type-I diabetes rats

Henry Cherng-Han Lin¹, Catherine Reena Paul², Chia-Hua Kuo³, Yung-Hsien Chang⁴, William Shao-Tsu Chen^5,⁶, Tsung-Jung Ho^7,^8,⁹, Cecilia Hsuan Day¹⁰, Vijaya Padma Viswanadha¹¹, Yuhsin Tsai¹², Chih-Yang Huang^2,^13,^14,^15,¹⁶

¹Graduate Institute of Chinese Medicine, China Medical University, Taichung 404, Taiwan
²Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan
³Laboratory of Exercise Biochemistry, University of Taipei, Taipei 11153, Taiwan
⁴Department of Chinese Medicine, China Medical University Hospital, China Medical University, Taichung 404, Taiwan
⁵Department of Psychiatry, Tzu Chi General Hospital, Hualien 97004, Taiwan
⁶School of Medicine, Tzu Chi University, Hualien 97004, Taiwan
⁷Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien 97004, Taiwan
⁸Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan
⁹School of Post-Baccalaureate Chinese Medicine, College of Medicine, Tzu Chi University, Hualien 97004, Taiwan
¹⁰Department of Nursing, MeiHo University, Pingtung 912, Taiwan
¹¹Department of Biotechnology, Bharathiar University, Coimbatore 641046, India
¹²Graduate Institute of Chinese Medicine, China Medical University, Taichung 41354, Taiwan
¹³Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan
¹⁴Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien 970, Taiwan
¹⁵Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan
¹⁶Department of Biotechnology, Asia University, Taichung 413, Taiwan

* Equal contribution

Received: March 12, 2021Accepted: June 4, 2021Published: July 7, 2021

https://doi.org/10.18632/aging.203244

Copyright: © 2021 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Pathological manifestations in either heart or kidney impact the function of the other and form the basis for the development of cardiorenal syndrome. However, the mechanism or factors involved in such scenario are not completely elucidated. In our study, to find the correlation between late fetal gene expression in diabetic hearts and their influence on diabetic nephropathy, we created a rat model with cardiac specific overexpression of IGF-IIRα, which is an alternative splicing variant of IGFIIR, expressed in pathological hearts. In this study, transgenic rats over expressing cardiac specific IGF-IIRα and non-transgenic animal models established in SD rats were administered with single dose of streptozotocin (STZ, 55 mg/Kg) to induce Type I diabetes. The correlation between IGF-IIRα and kidney damages were further determined based on their intensity of damage in the kidneys. The results show that cardiac specific overexpression of IGF-IIRα elevates the diabetes associated inflammation and morphological changes in the kidneys. The diabetic transgenic rats showed advancement in the pathological features such a renal tubular damage, collagen accumulation and enhancement in STAT3 associated mechanism of renal fibrosis. The results therefore show that that IGF-IIRα expression in the heart during pathological condition may worsen symptoms of diabetic nephropathy in rats.