Induction of fgf-7 (keratinocyte growth factor) after kidney
damage: a possible paracrine mechanism for tubule repair.
Ichimura, Takaharu, Paul W. Finch, Guohong Zhang, Mikio Kan, and James
L. Stevens.
The W. Alton Jones Cell Science Center, Old Barn Road, Lake Placid,
NY 12946, Phone: 518-523-1253, FAX: 518-523-1849, Derald H.
Ruttenberg Cancer Center, Mt. Sinai School of Medicine, Box 1130, 1
Gustave Levy Place, New York, NY 10029-6574
APStracts 3:0125F, 1996.
Keratinocyte growth factor (FGF-7), a member of the fibroblast growth
factor (FGF) family, 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 (OSOM). Interstitial FGF-7
expression increased throughout the kidney one 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 proximal tubule
epithelial cells (RPTE) 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.
Received 19 January 1996; accepted in final form 11 July 1996.
APS Manuscript Number F21-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996