Abstract
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.
Highlights
Present in the mediumbut intracellular fibroblast (heparin-binding) growth factor type-1 (FGF-1) was In our studies, transforminggrowth factor-a is notmitogenic released from rat kidney proximal tubuleepithelial cells (RPTE) byscrape wounding
FGF family, FGF-1 andFGF-2(basic), havebeen model to investigate the repair of chemicaldamage to the suggested to play a role in wound repair, inflammation, transproximaltubuleepithelium [1].Ingeneral,damagetothe formation, and angiogenesis [23, 24,26, 27]
These results suggest that FGF-1 expressionincreasesinprimaryculture of RPTE
Summary
IN VITRO AND (Received for publication, December 1, 1992, and in revised form, February 22, 1993). The regenerating proximal tubule epithelium in the rat has striking similarity with rat kidney proximal tubuleepithelial cells (RPTE)in primary culture 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. There is littledetailed knowledge about the role that changes ingrowth factor expression in thekidney might play in specific aspects of the nephrogenic repair process. Kidneyexpressesgrowth factors which creased in regenerating proximal tubuleepithelial cells could play an importantrole in proximal tubule epitheliaclell. The data suggest that autocrine expression of FGF-1 by regenerating proximal tubule epithelial cells plays a role in the regulation of nephrogenic repair.
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