Regulation of alpha-smooth muscle actin and CRBP-1 expression by retinoic acid and TGF-beta in cultured fibroblasts

J Cell Physiol. 2001 Jun;187(3):315-25. doi: 10.1002/jcp.1078.

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 alpha-smooth muscle actin. In fibroblasts cultured from different tissues we have shown that alpha-smooth muscle actin expression, mainly controlled by Transforming Growth Factor-beta (TGF-beta), is also regulated by retinoic acid and that CRBP-1, known to be a retinoic acid-responsive gene, is modulated by TGF-beta. The aim of the present study has been to investigate the relationships between retinoic acid and TGF-beta in regulating the expression of CRBP-1 and alpha-smooth muscle actin in cultured rat subcutaneous tissue fibroblasts. We have observed that the TGF-beta-induced, but not the retinoic acid-induced, alpha-smooth muscle actin expression is associated with a modulation of endogenous TGF-beta and TGF-beta receptors, suggesting that the action of retinoic acid on alpha-smooth muscle actin expression is not mediated by TGF-beta. The expression of CRBP-1 is regulated at the transcriptional level by TGF-beta and retinoic acid but not synergistically, suggesting a possible common pathway. However, retinoic acid, but not TGF-beta, increases the transcription of a transiently transfected chimeric construct containing the retinoic acid response element of the CRBP-1 promoter, indicating that TGF-beta 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / biosynthesis*
  • Actins / genetics
  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Gene Expression Regulation / drug effects
  • Promoter Regions, Genetic
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Wistar
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Retinol-Binding Proteins / biosynthesis*
  • Retinol-Binding Proteins / genetics
  • Retinol-Binding Proteins, Cellular
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Tretinoin / metabolism*
  • Tretinoin / pharmacology

Substances

  • Actins
  • RNA, Messenger
  • Rbp1 protein, rat
  • Recombinant Fusion Proteins
  • Retinol-Binding Proteins
  • Retinol-Binding Proteins, Cellular
  • Transforming Growth Factor beta
  • Tretinoin