Adipose-Derived Mesenchymal Stem Cells Transplantation Alleviates Renal Injury in Streptozotocin-Induced Diabetic Nephropathy.

Abstract

Previous studies have illustrated that bone marrow-derived mesenchymal stem cell (BMMSC) transplantation has therapeutic effects on diabetes and can prevent mice from renal damage and diabetic nephropathy (DN). Moreover, adipose-derived MSCs possess similar characteristics to BMMSCs. We investigated the effect of ADMSC transplantation on streptozotocin (STZ)-induced renal injury. Diabetes was induced in rats by STZ injection. After ADMSC treatment, renal histological changes and cell apoptosis were evaluated as were the expression of apoptosis-related proteins, Wnt/β-catenin pathway members, and klotho levels. We found that ADMSCs improved renal histological changes. Next, NRK-52E cells were exposed to normal glucose (NG; 5.5 mM glucose plus 24.5 mM mannitol)/high glucose (HG) or ADMSCs, and then measured for changes in the aforementioned proteins. Similarly, changes in these proteins were also determined following transient transfection of klotho siRNA. We found that both ADMSC transplantation and co-incubation reduced the rate of cellular apoptosis, decreased Bax and Wnt/β-catenin levels, and elevated Bcl-2 and klotho levels. Interestingly, klotho knockdown reversed the effects of ADMSCs on the expression of apoptosis-related proteins and Wnt/β-catenin pathway members. Taken together, ADMSCs transplantation might attenuate renal injury in DN via activating klotho and inhibiting the Wnt/β-catenin pathway. This study may provide evidence for the treatment of DN using ADMSCs.