TGF-?1 impairs homocysteine metabolism in human renal cells: possible implications for transplantation

• Published in: Transplant international 2002-12, Vol.16 (12), p.843-848
• Main Authors: Sengoelge, G rkan, Kletzmayr, Josef, Papagiannopoulos, Menelaos, Bohle, Barbara, H rl, Walter H., F dinger, Manuela, Sunder-Plassmann, Gere
• Format: Article
• Language: English
• ISSN: 0934-0874; 1432-2277
• DOI: 10.1007/s00147-003-0622-2

We hypothesized that TGF-[beta]1 influences the metabolism of homocysteine (Hcy) and increases its cellular export, which may lead to hyperhomocysteinemia in patients with renal transplants. We exposed human renal proximal tubule epithelial cells (huRPTECs) to different concentrations of TGF-[beta]1, IL-1[alpha], IL-10, or methionine and measured total Hcy (tHcy) in culture supernatants. We then examined the relationship between plasma levels of tHcy and TGF-[beta]1 in renal graft recipients. In multivariate analysis, the factors mediator (TGF-[beta]1, IL-1[alpha], IL-10), mediator concentration, methionine concentration, and "mediator × concentration" interaction independently influenced tHcy concentrations in culture supernatants. A 31% increase in tHcy was observed after exposure of huRPTECs to TGF-[beta]1 compared to medium alone. However, TGF-[beta]1 plasma levels in kidney graft recipients showed no independent association with tHcy plasma concentrations. We demonstrated that the release of Hcy from huRPTECs is enhanced by TGF-[beta]1, but that TGF-[beta]1 plasma levels in renal graft recipients show no independent relationship with hyperhomocysteinemia.