Differential expression and biological activity of retinoic acid–induced TGFβ isoforms in embryonic palate mesenchymal cells
✍ Scribed by Paul Nugent; Linh Ma; Robert M. Greene
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 273 KB
- Volume
- 177
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
The effect of retinoic acid (RA) on TGF-b mRNA expression and protein production in murine embryonic palate mesenchymal (MEPM) cells was examined by Northern blotting and TGF-b bioassay in association with TGF-b isoform-specific neutralizing antibodies. Heat or acid activation was used to distinguish between latent and active TGF-b protein released into the culture medium. RA had little or no effect on TGF-b1 mRNA expression and protein production. In contrast, RA increased TGF-b2 and b3 protein released into the culture medium, the protein being mostly in an inactive or latent form. The amount of active TGF-b released was increased relative to the total increase in TGF-b released, suggesting that RA treatment stimulated activation of latent TGF-b. RA also increased TGF-b2 mRNA expression; we have previously shown that RA upregulates TGF-b3 mRNA in these cells. RA and TGF-b individually inhibited 3 H-thymidine incorporation into MEPM cell DNA, while, when administered simultaneously, they inhibited proliferative activity to a greater extent. Heat-or acid-activated conditioned medium (CM) from MEPM cells treated with RA was able to inhibit 3 H-thymidine incorporation into MEPM cell DNA to an extent greater than seen with RA treatment alone. Coincubation of heat-activated CM from RA-treated MEPM cells with pan-specific or TGF-b2 or b3-specific neutralizing antibodies partially relieved the inhibitory effect on 3 Hthymidine incorporation, suggesting that this proliferative response was due to RA-induced TGF-b. Simultaneous treatment with RA and TGF-b also stimulated gycosaminoglycan (GAG) synthesis to an extent greater than that seen with TGFb treatment alone, this despite the ability of RA to inhibit GAG synthesis. These data demonstrate a role for RA and RA-induced TGF-b in the regulation of palate cell proliferation and GAG synthesis and suggest a role for TGF-b in retinoidinduced cleft palate.