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.
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.
Zhang
G
G
W. Alton Jones Cell Science Center, Lake Placid, New York 12946.
Ichimura
T
T
Maier
J A
JA
Maciag
T
T
Stevens
J L
JL
D000818:Animals; D001681:Biological Assay; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000633:toxicity; D004730:Endothelium, Vascular / Q000502:physiology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016220:Fibroblast Growth Factor 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000633:toxicity*; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D012038:Regeneration; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014471:Umbilical Veins; D014947:Wounds and Injuries / Q000503:physiopathology; D005466:Fluorocarbons
D003545:Cysteine; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2; D006845:Hydrocarbons, Fluorinated; D012333:RNA, Messenger; D013936:Thymidine; C064116:S-(1,1,2,2-tetrafluoroethyl)cysteine; D005466:Fluorocarbons