Transforming growth factors β1, β2 and β3 and their receptors are diffderentially 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)-β1 treatments on the expression of TGF-β1-3 and TGF-βI and βII receptors in human peritoneal fibroblasts (HPF). TGF-β isoforms and their receptors have been implicated as mediators of the lealing process and adhesion development. Methods: HPF were cultured under normal and hypoxic condition, and treated with and without (1 ng/mL) TGF-β1 for 24 hr. Total RNA from each group was subjected to multiplex reverse transcriptase-polymerase chain reaction (RT/PCR) to quantitate TGF-β1-3 and TGF-βI and βII receptors messenger RNA (mRNA) levels. Results: Hypoxia resulted in a significant increase in TGF-β1 (26%; P < 0.05), TGF-βIR (34%; P < 0.05) and TGF-βIIR (29%; P < 0.05) mRNA levels, with no effect on TGF-β2 or β3. TGF-β1 treatment resulted in a significant increase in TGF-β1 (35%; P < 0.05), but a decrease in TGF-β2 (22%; P < 0.05) and no effect on TGF-β3, TGF-βIR or TGF-βIIR. Combined treatment of hypoxia and TGF-β1 caused a significant increase in TGF-β1 (37%; P < 0.05), TGF-β2 (12%; P < 0.05), TGF-βIR (32%; P < 0.05) and TGF-βIIR (34%; P < 0.05). There is no significant change in the mRNA levels of TGF-β3 in any of the treatments. Conclusion: Hypoxia and TGF-β1 treatments of cultured HPF modulate the expression of TGF-β1, β2 and β3 and their receptors βIR and βIIR by increasing the ratio of TGF-β1 and β2 to β3, thus favoring the development of peritoneal adhesion.