Overexpression of glutamine:fructose‐6‐phosphate‐amidotransferase induces transforming growth factor‐β1 synthesis in NIH‐3T3 fibroblasts

FEBS Letters

Weigert, Cora¹  Häring, Hans U.¹  Brodbeck, Katrin¹  Lehmann, Rainer¹  Schleicher, Erwin D.¹ 

[1] Department of Internal Medicine, Division of Endocrinology, Metabolism and Pathobiochemistry, University of Tübingen, Otfried-Müller-Straße 10, D-72076 Tübingen, Germany

关键词: Glutamine:fructose-6-phosphate-amidotransferase;    Hexosamine biosynthetic pathway;    Transforming growth factor β;    Diabetic nephropathy;    Stable overexpression;    Fibroblast;    GAPDH;    glyceraldehyde-3-phosphate dehydrogenase;    GFAT;    glutamine:fructose-6-phosphate-amidotransferase;    GlcN-6-P;    glucosamine-6-phosphate;    SDS;    sodium dodecyl sulfate;    Sp1;    stimulatory protein 1;    SSC;    sodium chloride sodium citrate;    TGF-β1;    transforming growth factor β1;    UDP-GlcNAc;    uridine-5-diphosphate-N-acetylglucosamine;   

DOI  :  10.1016/S0014-5793(00)02395-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Increased flux through the hexosamine biosynthetic pathway with glutamine:fructose-6-phosphate-amidotransferase (GFAT) as rate-limiting enzyme has been linked to the enhanced bioactivity of the prosclerotic cytokine transforming growth factor β1 (TGF-β1) in fibrotic complications, particularly in diabetic kidney disease. Here, we investigate in a stable transfection system the effect of overexpression of GFAT on TGF-β1 synthesis in NIH-3T3 fibroblasts. We demonstrate a 1.8-fold stimulation of TGF-β1 mRNA and a 1.9-fold increased protein expression, whereas TGF-β2 production was not upregulated. The 1.5-fold enhanced TGF-β1 promoter activity suggests a transcriptional regulation. The elevated TGF-β1 protein is biologically active since GFAT-overexpressing cells exhibit a 2-fold fibronectin production. The results indicate a GFAT-dependent induction of TGF-β1 synthesis.

【 授权许可】

Unknown