The fibronectin production is increased by thrombospondin via activation of TGF-beta in cultured human mesangial cells.

Abstract:

:Thrombospondin (TSP) is a multifunctional glycoprotein that is synthesized by a variety of cells including mesangial cells (MCs). To clarify the effect of TSP on the pathogenesis of diabetic nephropathy, we studied the effect of glucose concentrations on TSP synthesis in cultured human MCs. Thereafter, the effects of TSP on the activation of transforming growth factor beta (TGF-beta) and fibronectin production were investigated in MCs. Incubating MCs with elevated glucose levels for 6 days resulted in an increase in TSP synthesis, measured by an enzyme-linked immunosorbent assay, both in culture media and cell layers. Treatment of MCs with TSP (final concentrations 1 and 5 microg/ml) for 24 h resulted in an increase (1.3- and 2.1-fold, respectively) in active TGF-beta, which was determined with an enzyme-linked immunosorbent assay using TGF-beta-soluble receptor type II, in the culture media without having any effect on the production of total TGF-beta. Exposure of MCs to TSP caused enhancement of fibronectin production in both media and cell layers in a TSP dose-dependent manner with the maximum at a TSP concentration of 1 microg/ml. The TSP-induced increase in fibronectin production from MCs was completely prevented by concomitant treatment with 10 microg/ml anti-TGF-beta neutralizing antibody. These results indicate that the TSP production is promoted by a high ambient glucose concentration in human MCs and that TSP, in turn, causes an increase in fibronectin production via activation of TGF-beta.

journal_name

Nephron

journal_title

Nephron

authors

Tada H,Isogai S

doi

10.1159/000044989

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

38-43

issue

1

eissn

1660-8151

issn

2235-3186

pii

nef79038

journal_volume

79

pub_type

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