RB3通过调节Akt/PKB通路介导白蛋白超负荷诱导的近端肾小管细胞凋亡

lbuminuria contributes to the development of chronic kidney disease (CKD), but the mechanisms are not fully understood. TRB3 is a kinase-like molecule that modifies cellular survival and metabolism and interferes with signal transduction pathways. We sought to determine whether TRB3 participates in apoptosis of renal proximal tubular cells stimulated by albumin overload. NRK-52E cells, a rat proximal tubular cell line, were incubated with various concentrations of fatty acid and endotoxin-free bovine serum albumin(BSA) for a variety of durations. Quantitative real-time PCR and western blot were used to determine TRB3 mRNA and protein expression separately. Apoptosis was detected by ssDNA ELISA assay and caspase3 activity measurement. Then gene silencing was used to investigate whether TRB3 participated in apoptosis of NRK-52E cells induced by BSA and through what signaling pathway it works. We found that BSA induced apoptosis in a time- and dose-dependent manner in NRK-52E cells. TRB3 expression was detected elevated after BSA induction concomitant with increase in apoptosis which was however significantly abrogated after TRB3 silencing. We also found that exposure to high concentration of BSA suppressed the phosphorylation of Akt/PKB, but silencing of TRB3 reversed this suppression, following with attenuated apoptosis. In conclusion, TRB3 mediates apoptosis of NRK-52E cells induced by albumin-overload via inhibiting Akt/PKB phosphorylation.