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FGF-2, BMP-2, and BMP-4 regulate retinoid binding proteins and receptors in 3T3 cells
1Department of Pharmacology, Cornell University Medical College, New York, New York 10021, USA.
Abstract:
An Important part of intercellular signalling is the ability of responding cells to regulate multiple signal transduction pathways. Just as retinoic acid exposure alters expression of many peptide growth factors and their receptors, we have found that peptide growth factors alter the expression of cellular retinoic acid binding proteins (CRABPs) and retinoic acid receptors (RARs). FGF-2 (basic fibroblast growth factor) treatment of BALB 3T3 fibroblasts increased the level of CRABP I RNA, whereas bone morphogenetic protein (BMP)-2 and BMP-4 reduced this level as well as the levels of CRABP II and RAR beta 1/beta 3 transcripts. Regulation of the CRABP I gene by FGF-2 occurred posttranscriptionally by increasing RNA stability. However, BMP-2 down-regulated CRABP I message without affecting message stability. Neither of these mechanisms was dominant, with intermediate levels of CRABP I RNA occurring in the presence of both FGF-2 and BMP-2 or BMP-4. These two different modes of regulation thus allow different levels of CRABP I RNA accumulation in the presence of different ratios of FGF-2 and BMP-2 or BMP-4.
Insights
Peptide growth factors, such as FGF-2 and BMPs, regulate cellular retinoic acid binding proteins (CRABPs) and receptors (RARs). FGF-2 increases CRABP I RNA stability, while BMPs decrease CRABP I, CRABP II, and RAR levels.
Area of Science:
- Cell Biology
- Molecular Biology
- Signal Transduction
Background:
- Intercellular signaling involves regulating multiple signal transduction pathways.
- Retinoic acid (RA) influences peptide growth factor and receptor expression.
- Peptide growth factors reciprocally affect cellular retinoic acid binding proteins (CRABPs) and retinoic acid receptors (RARs).
Purpose of the Study:
- To investigate how peptide growth factors modulate CRABP and RAR expression.
- To elucidate the regulatory mechanisms employed by FGF-2 and BMPs on CRABP I gene expression.
Main Methods:
- Treatment of BALB 3T3 fibroblasts with FGF-2, BMP-2, and BMP-4.
- Quantification of CRABP I, CRABP II, and RAR beta 1/beta 3 RNA levels.
- Assessment of RNA stability to determine posttranscriptional regulation.
Main Results:
- FGF-2 treatment increased CRABP I RNA levels by enhancing RNA stability.
- BMP-2 and BMP-4 decreased CRABP I, CRABP II, and RAR beta 1/beta 3 RNA levels.
- BMP-2 regulated CRABP I expression posttranscriptionally without affecting RNA stability.
- Combined FGF-2 and BMP treatment resulted in intermediate CRABP I RNA levels, indicating complex regulatory interactions.
Conclusions:
- Peptide growth factors FGF-2 and BMPs differentially regulate CRABP and RAR expression.
- Distinct posttranscriptional mechanisms (RNA stability vs. direct downregulation) mediate these effects.
- The interplay between FGF-2 and BMPs allows for fine-tuning of CRABP I RNA levels in response to varying signaling inputs.