TGF-beta1 impairs homocysteine metabolism in human renal cells: possible implications for transplantation.
We hypothesized that TGF-beta1 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-beta1, IL-1alpha, IL-10, or methionine and measured total Hcy (tHcy) in culture supernatants. We then examined the relationship between plasma levels of tHcy and TGF-beta1 in renal graft recipients. In multivariate analysis, the factors mediator (TGF-beta1, IL-1alpha, IL-10), mediator concentration, methionine concentration, and "mediator x concentration" interaction independently influenced tHcy concentrations in culture supernatants. A 31% increase in tHcy was observed after exposure of huRPTECs to TGF-beta1 compared to medium alone. However, TGF-beta1 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-beta1, but that TGF-beta1 plasma levels in renal graft recipients show no independent relationship with hyperhomocysteinemia.
Sengoelge
Gürkan
G
Department of Internal Medicine III, Division of Nephrology and Dialysis, University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Kletzmayr
Josef
J
Papagiannopoulos
Menelaos
M
Bohle
Barbara
B
Hörl
Walter H
WH
Födinger
Manuela
M
Sunder-Plassmann
Gere
G
D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D016030:Kidney Transplantation; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D011237:Predictive Value of Tests; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D007375:Interleukin-1; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D006710:Homocysteine; D016753:Interleukin-10