Sodium-dependent phosphate co-transporter type IIb associates with glomerular podocyte apoptosis and injury through regulating p38 MAPK/JNK signaling pathway in mice diabetic nephropathy

Objective: During the past decades, emerging experimental evidences had shown the important role of the sodium-dependent phosphate co-transporter type IIb (Npt2b) in phosphate absorption and hyperphosphatemia. This study was designed to evaluate the role of Npt2b in podocyte apoptosis induced glomerular injury in diabetic nephropathy. Methods: Male wile type and Npt2b knockout C57BL/6L mice were fed with high fat food, kidney change were detected, cell apoptosis related proteins and podocyte apoptosis percentage was evaluated to investigate the effect of Npt2b deletion on pathogenesis of glomerular injury in diabetic nephropathy. Results: Upregulation of Npt2b expression was confirmed in animal models fed with high fat food and primary podocytes incubated with high glucose, as compared with control, respectively. Npt2b knockout attenuated glomerular injury in mice model. Moreover, high glucose medium treated podocytes showed lower apoptosis percentage, companied with decrease in apoptosis related proteins (i.e. AIF, cleaved Caspase-3, Bax, p-p38, and p-JNK) and upregulation of Bcl-2. Conclusion: In conclusion, we confirmed that Npt2b expression in small intestine contributed to glomerular injury in diabetic nephropathy via modulating podocyte apoptosis through modulation of p38 MAPK/JNK signaling pathway. Npt2b siRNA in small intestine might be used as a potential management for preventing diabetic nephropathy.