Apoptosis and proliferation of human peritoneal fibroblasts in response to hypoxia.

OBJECTIVE

To determine the effect of hypoxia on apoptosis and proliferation of fibroblasts cultured from normal peritoneum or adhesions.

DESIGN

Prospective experimental study.

SETTING

University medical center.

PATIENT(S): Primary cultures of fibroblasts established from peritoneal and adhesion tissues of the same patients.

INTERVENTION(S): Hypoxia treatment of the primary cultured fibroblasts.

MAIN OUTCOME MEASURE(S): Apoptosis was assessed by the TUNEL assay and by the BCL-2-BAX expression ratio, as determined using multiplex reverse transcription polymerase chain reaction. The proliferation rate of these cells was determined by measuring the proliferative fraction using the flow cytometry in adhesion and peritoneal fibroblasts under normal and hypoxic conditions.

RESULT(S): Compared with fibroblasts from normal peritoneum, fibroblasts from adhesions had significant complementary decreases in apoptosis and an increase in proliferation. In response to hypoxia, the Bcl-2-bax mRNA ratio was significantly higher in fibroblasts from adhesions as compared with fibroblasts from normal peritoneum. The degree of apoptosis induced by hypoxia correlated with the increase in the bcl-2-bax ratio in fibroblasts derived from both normal peritoneum and adhesions.

CONCLUSION(S): Hypoxia induces proliferation while inhibiting apoptosis in fibroblasts from adhesion, thereby creating a phenotype that would favor adhesion development.