Rana Keyhanmanesh - Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Gholamreza Hamidian - Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
hajie lotfi - Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Zohre Zavari - Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Monireh Seyfollahzadeh - Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Afsane Ghadiri - Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Mehdi Ahmadi - Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Farzad Bahari - Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Fariba Mirzaei Bavil - Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

Objective: Nephropathy is known to be the leading cause of kidney failure in diabetic patients. Troxerutin, as a flavonoid component, could provide a novel protective strategy in the prevention of diabetic nephropathy. A large number of reports on the salutary effects of troxerutin inspired us to investigate its effect on the nephropathy signaling events (i.e., expression of TGF-β, miRNA۱۹۲, and SIP۱) in type-۱ induced diabetic rats.Materials and Methods: ۵۰ male Wistar rats were divided into ۵ groups including control group, sham group treated with troxerutin for ۴ weeks, diabetic group induced by streptozotocin (STZ) injection, DI group including insulin-treated diabetic animals and DT group treated with troxerutin. Ultimately, rat kidneys were extracted, and the level of miR-۱۹۲ (using qPCR), transforming growth factor-beta (TGF-β), and smad interacting protein ۱ (SIP۱) using an ELISA kit, was measured.Results: The level of TGF-β and miRNA۱۹۲ significantly increased in the diabetic group. However, their expression levels decreased following the administration of troxerutin and insulin (p<۰.۰۵) compared to control group. SIP۱ was down-regulated in the diabetic group, whereas a spike in the expression levels was observed after troxerutin administration compared to control and troxerutin groups (p<۰.۰۵). However, no significant difference was found in the effects of insulin and troxerutin on the level of miR-۱۹۲, SIP۱, and TGF- β.Conclusion: According to the previous literatures, during the progression of nephropathy, TGF-β represses SIP۱ (the repression region in the collagen gene) by increasing the expression of miR-۱۹۲. Ultimately, in this study, diabetes led to up-regulation of TGF-β while troxerutin proved to have a protective effect on the kidney by increasing SIP and lowering miR-۱۹۲ levels.

Diabetes, Troxerutin, miRNA۱۹۲, Nephropathy, TGF-β, SIP۱