Hepatocyte growth factor induces tubulogenesis of primary renal proximal tubular epithelial cells.
Hepatocyte growth factor (HGF)-induced tubulogenesis has been demonstrated with renal epithelial cell lines grown in collagen gels but not with primary cultured renal proximal tubular epithelial cells (RPTEs). We show that HGF selectively induces proliferation and branching morphogenesis of primary cultured rat RPTEs. Additional growth factors including fibroblast growth factor (FGF)-1, epidermal growth factor (EGF), FGF-7, or insulin-like growth factor-1 (IGF-1) did not selectively induce tubulogenesis. However, when administered in combination, these factors initiated branching morphogenesis comparable to HGF alone and greatly augmented HGF-induced proliferation and branching. Microscopic analysis revealed that branching RPTEs were undergoing tubulogenesis and formed a polarized epithelium. TGF-beta1 blocked HGF- or growth factor cocktail (GFC; HGF, FGF-1, EGF, IGF-1)-induced proliferation and branching morphogenesis. Adding TGF-beta1 after GFC-induced tubulogenesis had occurred caused a progressive regression of the tubular structures, a response associated with an increase in apoptosis of the RPTEs. Primary cultured RPTEs are capable of undergoing HGF-induced tubulogenesis. Unlike cell lines, combinations of growth factors differentially augment the response.
Bowes
R C
RC
Campbell University School of Pharmacy, Department of Pharmaceutical Sciences, Buies Creek, North Carolina 27506, USA. bowes@mailcenter.campbell.edu
Lightfoot
R T
RT
Van De Water
B
B
Stevens
J L
JL
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D016220:Fibroblast Growth Factor 1; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005782:Gels; D006133:Growth Substances / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011916:Rats, Inbred F344; D013936:Thymidine / Q000378:metabolism / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014316:Tritium
C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D005782:Gels; D006133:Growth Substances; D016212:Transforming Growth Factor beta; D014316:Tritium; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D013936:Thymidine