Transforming growth factor-beta inhibits phosphate transport in renal epithelial cells.
The effect(s) of transforming growth factor-beta (TGF-beta) on Pi transport was investigated in confluent opossum kidney (OK) epithelial cells. TGF-beta induced a time- and concentration-dependent decrease in the initial rate of sodium-dependent Pi, but not alanine, transport. This selective inhibitory effect on Pi transport was largely reversible and was not associated with a rise in adenosine 3',5'-cyclic monophosphate production. The reduction in Pi uptake was also independent of changes in extracellular calcium concentrations and prostaglandin synthesis. TGF-beta-mediated Pi transport inhibition appeared to involve neither pertussis toxin-sensitive G protein(s) nor augmented protein kinase C activity. However, the probable role of a serine/threonine protein kinase in signal transduction was supported by the considerable attenuation of TGF-beta effect by H-7. Furthermore, the TGF-beta-induced Pi transport reduction was blunted by cycloheximide and abolished by actinomycin D. In conclusion, TGF-beta selectively inhibits the activity of the sodium-dependent Pi transport system present in the apical membrane of renal epithelial cells. This action appears to be exerted via an unprecedented inhibitory pathway that might involve a serine/threonine protein kinase and alterations in the transcriptional and translational processes.
Law
F
F
Department of Medicine, University Hospital, Geneva, Switzerland.
Rizzoli
R
R
Bonjour
J P
JP
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology; D007668:Kidney / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D009893:Opossums; D010710:Phosphates / Q000493:pharmacokinetics*; D010879:Piperazines / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015398:Signal Transduction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007546:Isoquinolines; D010710:Phosphates; D010879:Piperazines; D016212:Transforming Growth Factor beta; D003609:Dactinomycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003513:Cycloheximide; D017346:Protein Serine-Threonine Kinases