Involvement of TGF-ß signal for peritoneal sclerosing in continuous ambulatory peritoneal dialysis

Background: Functional failure of the peritoneal membrane is the most serious problem in long-term continuous ambulatory peritoneal dialysis (CAPD). Transforming growth factor-beta (TGF-ß) is one of the key mediatorsof fibrosis in some organs, and is thought to be involved in peritoneal alterations. In this study, we examined the role of TGF-ß1/TGF-ß receptors for human peritoneal mesothelial cells (HPMCs) and fibroblasts, and their interactions in CAPD patients. Methods: HPMCs were cultured for 48h in a medium containing normal- dose glucose (7 mM), high-dose glucose (30 mM) and mannitol as an osmotic agent, equal to 30 mM glucose. Cell proliferation was observed using the Tetra Color One assay. The concentration of TGF-ß1 in culture supernatants was measured by enzyme-linked immunosorben assay (ELISA). The expression of TGF-ß receptor types I and II was observed by flow cytometry. HPMCs and fibroblasts were co-cultured and assayed using transwell inserts in order to identify the effects of the high-concentration glucose solution. Results: HPMC proliferation was inhibited by the high concentration of glucose but not by mannitol. The inhibition was abrogated by the neutralizing antibody for TGF-ß1. TGF-ß1 was induced by a high concentration of glucose but not by mannitol. The expression of both TGF-ß receptors was augmented in culture with the high concentration of glucose but not with mannitol. In the co-culture assay, the number of HPMCs was decreased and fibroblasts were significantly increased in culture with the high concentration of glucose. Conclusion: A high concentration of glucose induced a large amount of TGF-ß1 and enhanced the expression of TGFß receptors. HPMCs were sensitive to TGF-ß1 in response to a high concentration of glucose. These data suggest that TGF-ß1 from HPMCs exposed to a high concentration of glucose down-regulates the proliferation of HPMCs andaccelerates peritoneal fibrosis.