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J. Biol. Chem., Vol. 268, Issue 16, 11542-11547, Jun, 1993
G Zhang, T Ichimura, JA Maier, T Maciag and JL Stevens
The regenerating proximal tubule epithelium in the rat has striking
similarity with rat kidney proximal tubule epithelial cells (RPTE) in
primary culture (Wallin, A., Zhang, G., Jones, T. W., Jaken, S., and
Stevens, J. L. (1992) Lab. Invest. 66, 474-484). We used this in vitro
model to investigate mechanisms which may regulate aspects of nephrogenic
repair in vivo, and in particular the role of fibroblast (heparin-binding)
growth factor type-1 (FGF-1) expression. FGF-1 was present predominantly as
a 14.3-kDa polypeptide in rat kidney. Biological activity and mRNA for
FGF-1 increased dramatically in primary RPTE in culture along with an
increase in a 18.3-kDa FGF-1. Cycloheximide blocked FGF-1 expression in
primary culture indicating that the increase represents newly synthesized
factor rather than release from the extracellular matrix. The maximal
increase in expression occurs after the peak of RPTE proliferation.
Activity was not present in the medium but intracellular FGF-1 was released
from RPTE by scrape wounding. Immunohistochemical analysis showed that
FGF-1 expression increased in regenerating proximal tubule epithelial cells
5 days after nephrotoxic damage. Collectively, the data suggest that
autocrine expression of FGF-1 by regenerating proximal tubule epithelial
cells plays a role in the regulation of nephrogenic repair.
A role for fibroblast growth factor type-1 in nephrogenic repair. Autocrine expression in rat kidney proximal tubule epithelial cells in vitro and in the regenerating epithelium following nephrotoxic damage by S-(1,1,2,2-tetrafluoroethyl)-L-cysteine in vivo
W. Alton Jones Cell Science Center, Lake Placid, New York 12946.
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