Alteration of type I and III collagen expression in human peritoneal mesothelial cells in response to hypoxia and transforming growth factor-beta 1

Overexpression and accumulation of extracellular matrix is central to perit oneal adhesion formation following surgically induced tissue trauma. Transf orming growth factor-beta 1 and hypoxia have been implicated in tissue fibr osis and postoperative adhesion formation. To extend this observation we ex amined whether transforming growth factor-beta 1 and/or hypoxia regulate th e expression of type I and III collagen in human peritoneal mesothelial cel ls. Cultured human mesothelial cells were maintained under hypoxia (2% oxyg en), or treated with transforming growth factor-beta 1 (1 ng/ml) or a combi nation of hypoxia and transforming growth factor-beta 1. Total cellular RNA from treated and untreated cells were collected and subjected to multiplex reverse transcription/polymerase chain reaction to quantitate collagen I a nd III mRNA levels in response to these treatments. The results indicate th at 6 hours of hypoxia increased collagen III mRNA by 7.2 fold which was fur ther increased to 9.4 fold following transforming growth factor-beta 1 trea tment: in contrast collagen I mRNA decreased by 0.42 fold which was further decreased by 0.3 fold following transforming growth factor-beta 1 treatmen t. Transforming growth factor-beta 1 treatment under normal conditions resu lted in an 8.4-fold increase and a 0.3-fold decrease in collagen III and I mRNA levels, respectively. Hypoxia treatment also resulted in a 1.9-fold in crease in transforming growth factor-beta 1 mRNA level compared with contro l. The ratio of type III/I collagen was increased in response to transformi ng growth factor-beta 1 treatment under hypoxic condition. In conclusion, t he data suggest that hypoxia may modulate extracellular matrix production b y human mesothelial cells via a transforming growth factor-beta 1 dependent mechanism.