Protective effect of bone marrow mesenchymal stem cells modified with klotho on renal ischemia-reperfusion injury

Objective: To detect the combination protective effect of bone marrow mesenchymal stem cells (BMSCs) and Klotho gene on the renal ischemia-reperfusion injury (RIRI). Methods: BMSCs isolated from rats were transfected with Klotho gene to form BMSC(Kl). We injected BMSC(Kl) to allogenic rat RIRI model. After 24 h and 72 h, we detected the serum creatinine (SCr), malondialdehyde (MDA), and superoxide dismutase (SOD) in renal tissue, Hematoxylin-eosin (HE) staining, and TUNEL of renal pathology. The expression of FoxO1 and p-FoxO1 in post-hypoxia tubular epithelial cells of normal rat kidney (NRK-52E) were detected by Western blot after cocultured with BMSC(Kl). Results: Comparing with BMSC(Con) group, Rats in BMSC(Kl) group had lower SCr and MDA but higher SOD. Both HE and TUNEL score of renal tissue in BMSC(Kl) group were lower than that of BMSC(Con) group. Western blot indicated that FoxO1 was upregulated, while p-FoxO1 was downregulated in post-hypoxia NRK-52E cells. Conclusions: BMSCs transfected with Klotho gene can further ameliorate RIRI. The possible mechanism may be attributed to the upregulation of SOD in NRK-52E caused by Klotho-FoxO1 axis.