Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Nugent, P. et al.

TGF-beta modulates the expression of retinoic acid-induced RAR-beta in primary cultures of embryonic palate cells.

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.[1]

References

TGF-beta modulates the expression of retinoic acid-induced RAR-beta in primary cultures of embryonic palate cells. Nugent, P., Potchinsky, M., Lafferty, C., Greene, R.M. Exp. Cell Res. (1995) [Pubmed]

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