Increased decorin mRNA in diabetic mouse kidney and in mesangial and tubular cells cultured in high glucose.
The core protein of the proteoglycan decorin binds and neutralizes transforming growth factor-beta (TGF-beta). Activation of TGF-beta is crucial to tissue injury in diabetic nephropathy, but it is not currently known whether decorin plays a role in this disease. Mouse kidney cortex demonstrates more than a twofold increase in decorin mRNA after 1, 2, 3, and 6 wk of streptozotocin diabetes. Various mouse and rat renal cell types are studied in culture under normal or high-glucose conditions. Mouse glomerular mesangial and proximal tubular epithelial cells constitutively express decorin, and high glucose (450 mg/dl) increases decorin mRNA fourfold compared with 100 mg/dl glucose. Unlike rat mesangial cells, rat glomerular epithelial and endothelial cells do not constitutively express decorin, and no induction is observed in high glucose. When mouse mesangial and proximal tubular cells are exposed to TGF-beta1 (1 ng/ml), decorin mRNA is significantly decreased. Our findings suggest that the increased decorin expression in the diabetic kidney may counteract the hypertrophic and prosclerotic effects of increased TGF-beta levels and that a negative feedback loop may exist between decorin and TGF-beta.
Mogyorosi
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Renal-Electrolyte and Hypertension Division, Department of Medicine, and the Penn Center for the Molecular Studies of Kidney Diseases, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6144, USA.
Ziyadeh
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FN
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003470:Culture Media; D058575:Decorin; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D005260:Female; D005920:Glomerular Mesangium / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000096:biosynthesis*; D051381:Rats
D003470:Culture Media; C546879:Dcn protein, mouse; C546880:Dcn protein, rat; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D005947:Glucose