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.


METHODS
Tissue culture study.


METHODS
University research laboratory.


METHODS
Human fibroblasts cultures from normal peritoneum and adhesions that were exposed to dichloroacetic acid (DCA; 0 and 100 microg/mL) for 24 hours under normal and hypoxic conditions.


METHODS
Real-time reverse-transcription polymerase chain reaction of MMP-1, TIMP-1, and beta-actin.


RESULTS
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.


CONCLUSIONS
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.
Diamond
Michael P
MP
Department of Obstetrics and Gynecology, Wayne State University/Detroit Medical Center, Hutzel Hospital, Detroit, Michigan 48201, USA. mdiamond@med.wayne.edu
El-Hammady
Eslam
E
Wang
Rona
R
Saed
Ghassan
G
D015687:Cell Hypoxia; D002478:Cells, Cultured; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D000267:Tissue Adhesions / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D003999:Dichloroacetic Acid; D020781:Matrix Metalloproteinase 1