Graduate Institute of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan.
Aging (Albany NY). 2021 Jul 7;13(13):17536-17547. doi: 10.18632/aging.203244.
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.
在心脏或肾脏中的病理表现会影响另一个器官的功能，并构成心肾综合征发展的基础。然而，这种情况下涉及的机制或因素尚未完全阐明。在我们的研究中，为了寻找糖尿病心脏中晚期胎儿基因表达与糖尿病肾病之间的相关性，我们创建了一种心脏特异性过表达 IGF-IIRα 的大鼠模型，IGF-IIRα 是 IGFIIR 的一种选择性剪接变体，在病理性心脏中表达。在这项研究中，过表达心脏特异性 IGF-IIRα 的转基因大鼠和在 SD 大鼠中建立的非转基因动物模型接受单次链脲佐菌素 (STZ，55mg/kg) 注射以诱导 I 型糖尿病。进一步根据肾脏损伤的严重程度确定 IGF-IIRα 与肾脏损伤之间的相关性。结果表明，心脏特异性过表达 IGF-IIRα 会增加与糖尿病相关的炎症和肾脏形态变化。糖尿病转基因大鼠表现出肾脏小管损伤、胶原积累和 STAT3 相关肾纤维化机制增强等病理特征的进展。因此，结果表明，在病理条件下心脏中 IGF-IIRα 的表达可能会加重大鼠糖尿病肾病的症状。
