title: TGF-beta modulates the expression of retinoic acid-induced RAR-beta in primary cultures of embryonic palate cells.
abstract: We have previously shown that both transforming growth factor-beta (TGF-beta) and retinoic acid (RA) regulate the expression of cellular retinoic acid binding proteins (CRABP) I and II and TGF-beta 3 mRNAs in primary cultures of murine embryonic palate mesenchymal (MEPM) cells. We now describe additional cross-talk between the RA and TGF-beta signal transduction pathways--the ability of TGF-beta, including the endogenous form(s), to modulate the expression of the nuclear retinoic acid receptor-beta (RAR-beta). Northern blot hybridization revealed that RA induced the expression of RAR-beta mRNA, there being little or no detectable expression in untreated MEPM cells. Induction by 3.3 microM RA was abrogated by simultaneous treatment with TGF-beta 1 (5 ng/ml). TGF-beta 1 alone had no effect on RAR-beta mRNA expression. Determination of RAR-beta mRNA half-life by treatment with actinomycin D indicated that TGF-beta 1 did not alter the stability of RAR-beta mRNA. Conditioned medium (CM) from MEPM cells contained little active TGF-beta protein; heat treatment of the CM dramatically increased the amount of active TGF-beta as assessed by the mink lung epithelial cell bioassay. Furthermore, heat- or acid-activated CM also inhibited CRABP-I and RA-induced RAR-beta expression. The effect of heat-activated conditioned medium could be abrogated with panspecific neutralizing antibodies to TGF-beta, confirming that endogenous TGF-beta is the biologically active factor in heat-activated CM. These results provide evidence for complex interactions between TGF-beta and RA in the regulation of gene expression in embryonic palatal cells and suggest a role for endogenous TGF-beta in the regulation of expression of genes encoding elements of the RA signal transduction pathway.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: P
authors.initials: P
authors.lastname: Nugent
authors.forename: M
authors.initials: M
authors.lastname: Potchinsky
authors.forename: C
authors.initials: C
authors.lastname: Lafferty
authors.forename: R M
authors.initials: RM
authors.lastname: Greene
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D006207:Half-Life; D007700:Kinetics; D008168:Lung; D051379:Mice; D008813:Mice, Inbred ICR; D008907:Mink; D010159:Palate / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000096:biosynthesis*; D015183:Restriction Mapping; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D016212:Transforming Growth Factor beta; C082927:retinoic acid binding protein I, cellular; C082925:retinoic acid receptor beta; D003609:Dactinomycin; D014212:Tretinoin