Regulation of the expression and function of glucose transporter-1 by TGF-β1 and high glucose in mesangial cells |
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引用本文: | 章精,刘志红,刘浩,李颖健,黎磊石.Regulation of the expression and function of glucose transporter-1 by TGF-β1 and high glucose in mesangial cells[J].中华医学杂志(英文版),2000,113(6):508-513. |
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作者姓名: | 章精 刘志红 刘浩 李颖健 黎磊石 |
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作者单位: | ZHANG Jing,LIU Zhihong,LIU Hao,LI Yingjian and LI Leishi |
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基金项目: | ThisworkwassupportedbytheNationalNaturalScienceFoundationofChina!(No 39870288) |
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摘 要: | Objective To study the effects of high glucose and transforming growth factor-β1 (TGF-β1) on the expression and function of glucose transporter-1 (GLUT1) in mouse mesangial cells.Methods Cultured mouse mesangial cells were used.The expression of GLUT1 mRNA was detected by Northern Blot; glucose uptake and its kinetics were determined with a 2-Deoxy-[(3)H]-D-glucose uptake assay.Results Mesangial cells exposed to enriched glucose medium (20 mmol/L) for 72 hours demonstrated a decrease in both GLUT1 mRNA and V(max) for uptake of the glucose analog, 2-deoxy-D-glucose (2DOG), as compared to mesangial cells cultured in physiologic glucose concentrations(5.5 mmol/L).In contrast, hypertonic mannitol had no effect on GLUT1 mRNA levels.TGF-β1 treatment for 10 hours stimulated 2DOG uptake, both in 5.5 mmol/L and 20 mmol/L glucose medium, by approximately 4.28-fold in a dose-dependent manner (2 ng/ml maximum).Kinetic analysis of 2DOG uptake revealed an increase in V(max) and a decrease in K(m) in the presence of TGF-β1. TGF-β1 also up-regulated the expression of GLUT1 mRNA in mesangial cells.The addition of anti-TGF-β neutralizing antibody (30 μg/ml) in mesangial cells cultured in enriched glucose medium (20 mmol/L) led to a 40% decrease in 2DOG uptake.Conclusions The expression of GLUT1 can be suppressed by exposure of mesangial cells to high glucose medium, which may serve as a protective mechanism against possible adverse effects of excessive glucose flux into cells.TGF-β1 stimulates glucose uptake by enhancing the expression and function of GLUT1 in mesangial cells.This effect is independent of the glucose milieu in the cultured medium.
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关 键 词: | glucose transporter-1 hyperglycemia TGF-β1 mesangial cell diabetic nephropathy |
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