INDUCTION OF FGF-7 AFTER KIDNEY DAMAGE - A POSSIBLE PARACRINE MECHANISM FOR TUBULE REPAIR

A member of the fibroblast growth factor (FGF) family, keratinocyte gr owth factor (FGF-7), has unique specificity for epithelial cells. We i nvestigated the role of FGF-7 in repair of proximal tubular damage cau sed by S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC). In situ hybridi zation localized FGF-7 to interstitial cells in the medulla and outer stripe of the outer medulla. Interstitial FGF-7 expression increased t hroughout the kidney 1 day after TFEC treatment. FGFR2 IIIb mRNA. was high in the papilla and medulla and also increased after TFEC administ ration. By in situ hybridization, FGFR2 IIIb was localized to the tubu lar epithelium, particularly in collecting ducts. Proliferation of col lecting duct epithelial cells increased in adult kidney after damage t o the proximal tubule. FGFR2 IIIb, but not FGF-7, mRNA was also expres sed 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 par acrine growth factor loop. These results raise the possibility that a novel paracrine growth loop is activated by chemical damage and regula tes epithelial cell growth during tubular repair.