Regulation of transforming growth factor-beta, type III collagen, and fibronectin by dichloroacetic acid in human fibroblasts from normal peritoneum and adhesions

Fertil Steril. 2003 May;79(5):1161-7. doi: 10.1016/s0015-0282(03)00075-x.

Abstract

Objective: To examine the role of aerobic metabolism in fibroblasts from normal peritoneum and adhesions in the differential expression of extracellular matrix (ECM) and transforming growth factor-beta (TGF-beta), an inflammatory cytokine that regulates ECM expression.

Design: Cell culture under normoxic and hypoxic conditions.

Setting: University research laboratory.

Patient(s): Human fibroblasts cultures from normal peritoneum and adhesions.

Intervention(s): Exposure to dichloroacetic acid (DCA), which activates pyruvate dehydrogenase, for 24 hours under normal and hypoxic (2% O(2)) conditions.

Main outcome measure(s): Multiplex reverse transcriptase polymerase chain reaction (RT/PCR) of type III collagen, fibronectin, TGF-beta1, and beta-actin was performed, with analysis of PCR-amplified products performed by densimetric analysis of gel bands using the National Institutes of Health Image analysis program.

Result(s): DCA inhibited human peritoneal fibroblast and adhesion fibroblast TGF-beta1 mRNA expression under normoxic and hypoxic conditions. DCA also markedly reduced fibronectin and type III collagen expression under hypoxic conditions in fibroblasts from normal peritoneum and adhesions.

Conclusion(s): These observations provide further support for the suggestion that regulation of metabolic activity of peritoneal cells may provide a target for interventions designed to reduce postoperative adhesions.

MeSH terms

  • Cell Hypoxia
  • Cells, Cultured
  • Collagen Type III / genetics*
  • Dichloroacetic Acid / pharmacology*
  • Fibroblasts / metabolism
  • Fibronectins
  • Gene Expression Regulation / drug effects*
  • Humans
  • Peritoneum / cytology
  • Peritoneum / metabolism*
  • Postoperative Complications / prevention & control
  • RNA, Messenger / analysis
  • Tissue Adhesions / metabolism*
  • Tissue Adhesions / pathology
  • Tissue Adhesions / prevention & control
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta1

Substances

  • Collagen Type III
  • Fibronectins
  • RNA, Messenger
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Dichloroacetic Acid