FGF/FGFR2 Protects against Tubular Cell Death and Acute Kidney Injury Involving Erk1/2 Signaling Activation.

BACKGROUND

Fibroblast growth factors (FGFs) are heparin-binding proteins involved in a variety of biological processes, and part of them may act through binding with cell membrane receptor FGFR2.

OBJECTIVES

To clarify the role and mechanisms of FGFR2 signaling in tubular cell survival and acute kidney injury (AKI).

METHOD

In this study, kidney ischemia/reperfusion (IR) or cisplatin injection was used to induce AKI in mice.

RESULTS

In the kidneys after IR or cisplatin injection, the expression of FGFs and Erk1/2 phosphorylation were elevated. To investigate the role of FGFs in tubular cell survival and AKI, a mouse model with tubular cell specific FGFR2 gene disruption was generated. The knockouts were born normal. At 2 months of age, about one-third of the knockouts developed mild hydronephrosis. Ablation of FGFR2 in tubular cells aggravated acute kidney dysfunction as well as tubular cell apoptosis induced by IR or cisplatin. In addition, Erk1/2 phosphorylation was less in the knockout kidneys than in control littermates at day 1 after cisplatin injection. In cultured NRK-52E cells, recombinant FGF2 protein induced Erk1/2 phosphorylation and inhibited cisplatin-induced cell death. PD98059 abolished Erk1/2 phosphorylation and partly reversed the protective effect of FGF2 on cisplatin-induced cell death.

CONCLUSIONS

This study indicates that FGF/FGFR2 signaling plays an important role in protecting against tubular cell death and AKI, which is partly through stimulating Erk1/2 activation.