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

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-β), 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% O₂) conditions. Main Outcome Measure(s): Multiplex reverse transcriptase polymerase chain reaction (RT/PCR) of type III collagen, fibronectin, TGF-β1, and β-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-β1 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.