Effects of exosomes derived from kidney tubular cells on diabetic nephropathy in Rat

Objective: One of the severe complications and the popular causes of the end stage renal disease (ESRD) of diabetes mellitus is diabetic nephropathy (DN). Exosomes secreted from diverse cells have been regarded as one of the novel encouraging therapies for the chronic renal injuries. This study, tried to assess whether extracted exosomes from kidney tubular cells (KTCs) could prevent DN at early stage in vivo.Materials and Methods: Exosomes from conditioned medium of rabbit kidney tubular cells (RK۱۳; KTCs) have been isolated with the ultra-filtration combined purification procedures. For characterization of exosomes the assessment of morphology, size and particular biomarkers were done by using TEM, SEM, western bloting, AFM and zeta sizer nano analysis. Four groups of rats have been utilized, including the DN, control, DN treated with exosomes and sham group. After diabetes induction by streptozotocin (۵۰ mg/kg body weight) in rats, exosomes were injected weekly through the tail vein until ۶ weeks. Then ۲۴-hour urine protein, the blood urea nitrogen (BUN), and serum creatinine (Scr) have been measured through detection kits. The histopathological effects of exosomes on kidneys were evaluated by PAS staining and the expression of miRNAs ۲۹a and ۳۷۷ by using the Real time PCR Technique.Results: The sizes of KTCs-Exo were approximately ۵۰–۱۵۰ nm with spherical morphology, and expressed the specific markers of CD۹ and CD۶۳. Intravenous injections of KTCs-Exo potentially reduced the urine volume, protein ۲۴-hour, BUN, and Scr (P< ۰.۰۰۰۱, p < ۰.۰۱, p < ۰.۰۰۱, p < ۰.۰۰۰۱) and decreased the miRNA-۳۷۷ and increased miRNA-۲۹a (p <۰.۰۱ & p <۰.۰۰۱) in diabetic rats. In addition, the KTC-Exo ameliorated the renal histopathology with regulatory changes in microRNAs expression.Conclusion: KTC-Exo involve in attenuation kidney injury from diabetes by regulating the microRNAs associated with DN.

کلیدواژه ها:

Exosomes ، KTC-Exo ، Kidney ، miRNAs ، Diabetic nephropathy