Regulation of α‐smooth muscle actin and CRBP‐1 expression by retinoic acid and TGF‐β in cultured fibroblasts

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Abstract
We have reported that Cellular Retinol Binding Protein-1 (CRBP-1) is expressed de novo during skin wound healing by a proportion of fibroblastic cells which then differentiate into myofibroblasts and express α-smooth muscle actin. In fibroblasts cultured from different tissues we have shown that α-smooth muscle actin expression, mainly controlled by Transforming Growth Factor-β (TGF-β), is also regulated by retinoic acid and that CRBP-1, known to be a retinoic acid-responsive gene, is modulated by TGF-β. The aim of the present study has been to investigate the relationships between retinoic acid and TGF-β in regulating the expression of CRBP-1 and α-smooth muscle actin in cultured rat subcutaneous tissue fibroblasts. We have observed that the TGF-β-induced, but not the retinoic acid-induced, α-smooth muscle actin expression is associated with a modulation of endogenous TGF-β and TGF-β receptors, suggesting that the action of retinoic acid on α-smooth muscle actin expression is not mediated by TGF-β. The expression of CRBP-1 is regulated at the transcriptional level by TGF-β and retinoic acid but not synergistically, suggesting a possible common pathway. However, retinoic acid, but not TGF-β, increases the transcription of a transiently transfected chimeric construct containing the retinoic acid response element of the CRBP-1 promoter, indicating that TGF-β does not influence CRBP-1 through the retinoic acid pathway. Our results indicate that distinct pathways regulate the genes involved in the appearance and evolution of the myofibroblastic cells. The characterization of these pathways will be helpful for the design of drugs influencing wound healing.

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