The mTOR-RUNX1 pathway regulates DC-SIGN expression in renal tubular epithelial cells

Renal tubular epithelial cells (RTECs) play pivotal roles in the innate immune response in kidneys. Dendritic cell specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) functions as both the innate immune recognition receptor and the adhesion molecule. In our previous study, we found that DC-SIGN expression was induced in RTECs during renal inflammation. However, the underlying mechanism remains unclear. Here, we used the human renal proximal tubular epithelial cell lines (HK-2) to investigate the mechanism of TNF-α-induced expression of DC-SIGN. Our results showed that TNF-α up-regulated the expressions of DC-SIGN and Runt-related transcription factor 1 (RUNX1) in a time-dependent manner and that it up-regulated DC-SIGN promoter-driven luciferase activity in a dose-dependent manner. The mTOR inhibitor rapamycin and mTOR siRNA blocked the TNF-α-induced up-regulation of DC-SIGN expression. Meanwhile, DC-SIGN expression was also inhibited by RUNX1 siRNA and its inhibitor Ro5-3335. In addition, both mTOR and RUNX1 inhibitors attenuated TNF-α-induced the increase in DC-SIGN promoter-driven luciferase activity. Finally, we found that HK-2 cells exposed to rapamycin or mTOR siRNA reduced the TNF-α-induced up-regulation of RUNX1. In conclusion, these results indicated that the mTOR-RUNX1 pathway participates in the regulation of TNF-α-induced DC-SIGN expression in RTECs.