Bone marrow-derived c-kit positive stem cell administration protects against diabetes-induced nephropathy in a rat model by reversing PI3K/AKT/GSK-3? pathway and inhibiting cell apoptosis

Stem cell-based therapy has been proposed as a novel therapeutic strategy for diabetic nephropathy. This study was designed to evaluate the effect of systemic administration of rat bone marrow-derived c-kit positive (c-kit+) cells on diabetic nephropathy in male rats, focusing on PI3K/AKT/GSK-3 ss pathway and apoptosis as a possible therapeutic mechanism. Twenty-eight animals were randomly classified into four groups: Control group (C), diabetic group ( D), diabetic group, intravenously received 50 mu l phosphate-buffered saline (PBS) containing 3 x-10(5) c-kit- cells (D +ckit(-)); and diabetic group, intravenously received 50 mu l PBS containing 3 x10(5) c- Kit(-) positive cells (D +ckit(+)). Control and diabetic groups intravenously received 50 mu l PBS. C-kit+ cell therapy could reduce renal fibrosis, which was associated with attenuation of inflammation as indicated by decreased TNF-a and IL-6 levels in the kidney tissue. In addition, c-kit+ cells restored the expression levels of PI3K, pAKT, and GSK-3 ss proteins. Furthermore, renal apoptosis was decreased following c-kit+ cell therapy, evidenced by the lower apoptotic index in parallel with the increased Bcl-2 and decreased Bax and Caspase- 3 levels. Our results showed that in contrast to c-kit- cells, the administration of c-kit(+) cells ameliorate diabetic nephropathy and suggested that c-kit(+) cells could be an alternative cell source for attenuating diabetic nephropathy.