Induction of FGF-7 after kidney damage: a possible paracrine mechanism for tubule repair.

A member of the fibroblast growth factor (FGF) family, keratinocyte growth factor (FGF-7 has unique specificity for epithelial cells. We investigated the role of FGF-7 in repair of proximal tubular damage caused by S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC). In situ hybridization localized FGF-7 to interstitial cells in the medulla and outer stripe of the outer medulla. Interstitial FGF-7 expression increased throughout the kidney 1 day after TFEC treatment. FGFR2 IIIb mRNA was high in the papilla and medulla and also increased after TFEC administration. By in situ hybridization, FGFR2 IIIb was localized to the tubular epithelium, particularly in collecting ducts. Proliferation of collecting duct epithelial cells increased in adult kidney after damage to the proximal tubule. FGFR2 IIIb, but not FGF-7, mRNA was also expressed by rat proximal tubule epithelial (RPTE) cells in vitro, and FGF-7 increased DNA synthesis in RPTE. Thus FGFR2 IIIb and FGF-7 expression is segregated between epithelial and interstitial cells forming a paracrine growth factor loop. These results raise the possibility that a novel paracrine growth loop is activated by chemical damage and regulates epithelial cell growth during tubular repair.