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Interactions between the transforming growth factor beta (TGF beta) and retinoic acid signal transduction pathways in
1Department of Anatomy and Developmental Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Abstract:
Regulation of expression of transforming growth factor-beta 3 (TGF-beta 3) and the cellular retinoic acid-binding proteins-I and II (CRABP-I, -II) by retinoic acid (RA) and TGF-beta was examined in primary cultures of murine embryonic palate mesenchymal (MEPM) cells. Northern blot hybridization revealed that RA and TGF-beta 1, beta 2 and beta 3 stimulated the expression of TGF-beta 3 mRNA within 24 hours of treatment. RA down-regulated the expression of CRABP-I mRNA and up-regulated the expression of CRABP-II mRNA in a time- and dose-dependent fashion. TGF-beta 1, beta 2 and beta 3 also down-regulated the expression of CRABP-I mRNA, while epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) were without effect. TGF-beta 1 also stimulated a dose-dependent increase in the expression of CRABP-II mRNA. Again EGF and TGF-alpha were without effect. Basic fibroblast growth factor (bFGF) elicited a slight inhibitory effect on CRABP-II and a slight stimulatory effect on CRABP-I mRNA expression. Thus, cells derived from the mammalian developing palate express CRABP-I and CRABP-II mRNAs, both of which may be regulated by RA and TGF-beta. These data constitute the first demonstration of an effect of TGF-beta on the expression of CRABP-I and CRABP-II and provide further evidence for cross-talk between RA and TGF-beta signal transduction pathways.
Insights
Retinoic acid (RA) and transforming growth factor-beta (TGF-beta) regulate key gene expression in developing palate cells. This study reveals TGF-beta
Area of Science:
- Molecular Biology
- Developmental Biology
- Cell Signaling
Background:
- Palate development involves complex molecular signaling pathways.
- Transforming growth factor-beta (TGF-beta) and retinoic acid (RA) are crucial signaling molecules in embryonic development.
- Cellular retinoic acid-binding proteins (CRABP-I and CRABP-II) play roles in mediating RA effects.
Purpose of the Study:
- To investigate the regulation of TGF-beta 3 and CRABP-I/II gene expression by RA and TGF-beta in murine embryonic palate mesenchymal (MEPM) cells.
- To explore potential cross-talk between RA and TGF-beta signaling pathways in palate development.
Main Methods:
- Primary cultures of MEPM cells were treated with RA, TGF-beta isoforms (1, 2, 3), epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and basic fibroblast growth factor (bFGF).
- Gene expression levels of TGF-beta 3, CRABP-I, and CRABP-II mRNA were analyzed using Northern blot hybridization.
Main Results:
- RA and TGF-beta isoforms (1, 2, 3) significantly stimulated TGF-beta 3 mRNA expression within 24 hours.
- RA dose- and time-dependently down-regulated CRABP-I mRNA and up-regulated CRABP-II mRNA expression.
- TGF-beta isoforms also down-regulated CRABP-I mRNA expression, while TGF-beta 1 up-regulated CRABP-II mRNA expression. EGF and TGF-alpha had no effect.
Conclusions:
- Murine embryonic palate cells express CRABP-I and CRABP-II, and their expression is regulated by both RA and TGF-beta.
- These findings demonstrate, for the first time, the effect of TGF-beta on CRABP-I and CRABP-II expression.
- The results provide evidence for intricate cross-talk between RA and TGF-beta signaling pathways during palate development.