Transforming growth factor-beta modulates the parathyroid hormone-related protein-induced responses in renal epithelial cells.
PTH-related protein (PTHrP), the major mediator of hypercalcemia of malignancy, reduces tubular phosphate (Pi) reabsorption through its PTH-like renotropic actions. Another peptide detected in tumoral cells, transforming growth factor-beta (TGF beta), has been shown to considerably suppress the sodium-dependent Pi transport system present in the apical membrane of renal epithelial cells. The unexplored interactions between TGF beta and PTHrP were examined in opossum kidney (OK) cells. Using confluent OK cells, we showed that TGF beta attenuated the inhibition of Pi transport mediated by PTHrP. Similarly, 18 h TGF beta incubation resulted in a substantial reduction of the cAMP response elicited by PTHrP without apparent involvement of pertussis toxin-sensitive guanine nucleotide binding protein(s). The number of PTHrP(1-34) binding sites in TGF beta-treated cells was decreased with the affinity unchanged. Forskolin- and prostaglandin E2-stimulated cAMP productions were not significantly altered by TGF beta treatment. Therefore, TGF beta reduced Pi transport in OK cells, modulated the actions of PTHrP, and decreased its receptor number. Whether this happens in vivo is as yet unknown.
Department of Medicine, University Hospital, Geneva, Switzerland.
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D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology; D004347:Drug Interactions; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D009893:Opossums; D044162:Parathyroid Hormone-Related Protein; D010710:Phosphates / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D010710:Phosphates; D011506:Proteins; D016212:Transforming Growth Factor beta; D005576:Colforsin; D000242:Cyclic AMP; D015232:Dinoprostone