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-beta), an inflammatory cytokine that regulates ECM expression.


METHODS
Cell culture under normoxic and hypoxic conditions.


METHODS
University research laboratory.


METHODS
Human fibroblasts cultures from normal peritoneum and adhesions.


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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Diamond
Michael P
MP
Division of Reproductive Endocrinology and Infertility, 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; D024061:Collagen Type III / Q000235:genetics*; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism*; D011183:Postoperative Complications / Q000517:prevention & control; D012333:RNA, Messenger / Q000032:analysis; D000267:Tissue Adhesions / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D024061:Collagen Type III; D005353:Fibronectins; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003999:Dichloroacetic Acid