Transforming Growth Factor-Beta-1 Latency-Associated Peptide and Soluble Betaglycan Prevent a Glucose-Induced Increase in Fibronectin Production in Cultured Human Mesangial Cells

Abstract

This study was performed to investigate the effects of transforming growth factor-β1 (TGF-β1) latency-associated peptide (LAP) and betaglycan on TGF-β1 activity, and on the glucose-induced overproduction of fibronectin in cultured human mesangial cells (MCs). We found that recombinant LAP and recombinant soluble betaglycan decrease the active form of TGF-β1, measured by ELISA, in a dose-dependent manner in a cell-free system. The effective dosages of LAP and soluble betaglycan for a 50% reduction were approximately 20- and 75-fold of the TGF-β1 concentration, respectively. The active form of TGF-β1 in the media secreted from MCs was significantly (p < 0.01) reduced by the addition of 10 nmol/l LAP and 10 nmol/l soluble betaglycan with no significant change in total (active + latent) TGF-β1. Recombinant LAP and soluble betaglycan also inhibited a recombinant TGF-β1-stimulated increase in fibronectin production in MCs. Furthermore, the glucose-induced increase in fibronectin secreted from MCs was significantly (p < 0.01) suppressed by concomitant incubation with LAP or soluble betaglycan, while these agents had no effect on fibronectin production under physiological glucose concentrations. These results indicate that recombinant LAP and soluble betaglycan suppress the glucose-induced overproduction of fibronectin presumably via inhibition of TGF-β1 activity in MCs. Further in vivo studies are needed to define the possible beneficial effects of these agents in diabetic nephropathy.

Journal

Journal ID (publisher-id): NEF

Journal ID (nlm-ta): Nephron

Journal ID (doi): 10.1159/issn.1660-8151

Title: Nephron

Publisher: S. Karger AG

ISSN (Print): 1660-8151

ISSN (Electronic): 2235-3186

Publication date Subscription-year: 2002

Publication date (Print): August 2002

Publication date (Electronic): 15 July 2002

Volume: 91

Issue: 4

Pages: 606-611

Affiliations

^aResearch Division, Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, and ^bDepartment of Internal Medicine, Shironishi Hospital, Shironishi Medical Foundation, Tokyo, Japan

Article

Publisher ID: 65020 Other ID: Nephron 2002;91:606–611

DOI: 10.1159/000065020

PubMed ID: 12138262

Copyright statement: © 2002 S. Karger AG, Basel

License:

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Page count

Figures: 3, Tables: 1, References: 25, Pages: 6

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Categories

Subject: Original Paper