Transforming growth factor-beta-mediated proliferation of renal tubular epithelial cells involves pertussis toxin-sensitive G protein-and protein kinase C-dependent pathways.
Exposure of LLCPK-1 cells to transforming growth factor (TGF)-beta(1) resulted in an increase in [3H]thymidine incorporation. This increase depended on the concentration of TGF-beta(1) used with an EC50 value of 0.3-1 pmol/l. Concentrations > 10 pmol/l were inhibitory. Similar effects occurred with TGF-beta(3). Addition of both TGF-beta(1) and TGF-beta(3) together had no additive effect. Pretreatment of cells with 10 mumol/1 genestein exerted no effect on TGF-beta-mediated response, whereas pretreatment with 10 mumol/1 Ro-32-0432 inhibited TGF-beta-mediated [3H]thymidine incorporation. In addition, pretreatment of cells with pertussis toxin attenuated TGF-beta-mediated proliferation of LLCPK-1 cells. These data indicate that in LLCPK-1 cells, TGF-beta(1) and TGF-beta(3) mediate their responses through the same receptor. This pathway involves protein kinase C and pertussis toxin-sensitive G protein.
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
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D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*; D014316:Tritium; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007211:Indoles; D011758:Pyrroles; D016212:Transforming Growth Factor beta; D010566:Virulence Factors, Bordetella; D014316:Tritium; C085989:Ro 32-0432; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D013936:Thymidine