Regulation of matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1 by dichloroacetic acid in human fibroblasts from normal peritoneum and adhesions

Objective: To examine the role of stimulation of aerobic metabolism on the differential expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), which are differentially regulated in fibroblasts isolated from normal human peritoneum and adhesions. Design: Tissue culture study. Setting: University research laboratory. Patient(s): Human fibroblasts cultures from normal peritoneum and adhesions that were exposed to dichloroacetic acid (DCA; 0 and 100 μg/mL) for 24 hours under normal and hypoxic conditions. Intervention(s): Main outcome measure(s): Real-time reverse-transcription polymerase chain reaction of MMP-1, TIMP-1, and β-actin. Result(s): Dichloroacetic acid stimulated peritoneal fibroblast MMP-1 mRNA expression under normoxic conditions; this stimulation was lost during hypoxia. In adhesion fibroblasts, DCA increased MMP-1 mRNA expression; this effect was reversed by hypoxia. Expression of TIMP-1 mRNA was insignificantly increased by DCA in normal peritoneal and adhesion fibroblasts under normoxic conditions; however under hypoxic conditions, DCA reduced TIMP-1 mRNA expression from both. Conclusion(s): Regulation of metabolic activity of peritoneal cells may provide a target for future interventions for reduction of development of postoperative adhesions, particularly as it relates to healing of peritoneal sites that did not previously have adhesions as opposed to sites that underwent lysis of preexistent adhesions.