Transforming growth factors beta1, beta2 and beta3 and their receptors are differentially expressed in human peritoneal fibroblasts in response to hypoxia.

PROBLEM

Little is known about the role of peritoneal fibroblasts in adhesion formation. This study determines the effect of hypoxia and transforming growth factor (TGF)-beta1 treatment on the expression of TGF-beta1-3 and TGF-betaI and betaII receptors in human peritoneal fibroblasts (HPF). TGF-beta isoforms and their receptors have been implicated as mediators of the healing process and adhesion development.

METHODS

HPF were cultured under normal and hypoxic condition, and treated with and without (1 ng/mL) TGF-beta1 for 24 hr. Total RNA from each group was subjected to multiplex reverse transcriptase-polymerase chain reaction (RT/PCR) to quantitate TGF-beta1-3 and TGF-betaI and betaII receptors messenger RNA (mRNA) levels.

RESULTS

Hypoxia resulted in a significant increase in TGF-beta1 (26%; P < 0.05), TGF-betaIR (34%; P < 0.05) and TGF-betaIIR (29%; P < 0.05) mRNA levels, with no effect on TGF-beta2 or beta3. TGF-beta1 treatment resulted in a significant increase in TGF-beta1 (35%; P < 0.05), but a decrease in TGF-beta2 (22%; P < 0.05) and no effect on TGF-beta3, TGF-betaIR or TGF-betaIIR. Combined treatment of hypoxia and TGF-beta1 caused a significant increase in TGF-beta1 (37%; P < 0.05), TGF-beta2 (12%; P < 0.05), TGF-betaIR (32%; P < 0.05) and TGF-betaIIR (34%; P < 0.05). There is no significant change in the mRNA levels of TGF-beta3 in any of the treatments.

CONCLUSION

Hypoxia and TGF-beta1 treatments of cultured HPF modulate the expression of TGF-beta1, beta2 and beta3 and their receptors betaIR and betaIIR by increasing the ratio of TGF-beta1 and beta2 to beta3, thus favoring the development of peritoneal adhesion.