STAT3 inhibits apoptosis of human renal tubular epithelial cells induced by ATP depletion/recovery.

BACKGROUND/AIMS: Apoptosis has been implicated in renal ischemic injury, the regulating mechanism of which is still unclear. Signal transducers and activators of transcription (STAT) participate in inflammation, apoptosis, and tumorigenesis. In the in vitro model of renal ischemic injury, we explored the role of the STAT3, a major component of the STAT family, in apoptosis of human proximal tubular epithelial cell (HKC) induced by ATP depletion/recovery.

METHODS

Apoptosis of HKC was induced in an in vitro model of acute renal failure. STAT3 activation was analyzed by Western blotting. RNA interference was used to knock down STAT3 expression. The effect of STAT3 knockdown or STAT3C overexpression on apoptosis was assessed by annexin V binding and propidium iodide uptake.

RESULTS

STAT3 was phosphorylated during the course of ATP depletion-induced HKC cell apoptosis. STAT3 knockdown suppressed STAT3 phosphorylation, and promoted apoptosis of HKC subjected to ATP depletion/recovery, while STAT3C overexpression conferred resistance of HKC to ATP depletion-induced apoptosis.

CONCLUSION

Our results demonstrated that STAT3 mediates resistance to ATP depletion-induced apoptosis of HKC, which may be a potential target in treatment of renal ischemic injury.