Evidence linking glycated albumin to altered glomerular nephrin and VEGF expression, proteinuria, and diabetic nephropathy
| Autor: | Clyde W. Shearman, Gregory T. Lautenslager, Fuad N. Ziyadeh, Sheldon Chen, Margo P. Cohen, Elizabeth Hud, Elizabeth Shea |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Collagen Type IV
Glycation End Products Advanced Male Vascular Endothelial Growth Factor A medicine.medical_specialty Kidney Glomerulus Fluorescent Antibody Technique urologic and male genital diseases Podocyte Nephrin Diabetic nephropathy Transforming Growth Factor beta1 chemistry.chemical_compound Mice Transforming Growth Factor beta Internal medicine Medicine Albuminuria Animals Diabetic Nephropathies Glycated Serum Albumin Serum Albumin Proteinuria biology business.industry urogenital system diabetic nephropathy Albumin Glomerulosclerosis Membrane Proteins nephrin medicine.disease VEGF Mice Mutant Strains female genital diseases and pregnancy complications Vascular endothelial growth factor medicine.anatomical_structure Endocrinology chemistry Nephrology biology.protein glycated albumin medicine.symptom business |
| Zdroj: | Kidney International. 68(4):1554-1561 |
| ISSN: | 0085-2538 |
| DOI: | 10.1111/j.1523-1755.2005.00567.x |
| Popis: | Evidence linking glycated albumin to altered glomerular nephrin and VEGF expression, proteinuria, and diabetic nephropathy. Background Albumin modified by Amadori-glucose adducts has been linked to the development of diabetic nephropathy through its ability, independent of hyperglycemia, to activate protein kinase C-β (PKC-β), up-regulate the transforming growth factor-β (TGF-β) system, and stimulate expression of extracellular matrix proteins in glomerular cells, and by the demonstration that reducing the burden of glycated albumin ameliorates renal structural and functional abnormalities in the db/db mouse. Methods To probe whether the salutary effects consequent to lowering glycated albumin, which include reduction of albuminuria, relate to an influence of the Amadori-modified protein on nephrin, the podocyte protein critical to regulation of protein excretion, and on the angiogenic vascular endothelial growth factor (VEGF), which induces microvascular permeability, diabetic db/db mice were treated with a small molecule that inhibits the nonenzymatic glycation of albumin. Results Compared to nondiabetic db/m mice, diabetic controls exhibited increased urinary excretion of albumin and type IV collagen, elevated renal TGF-β1 protein levels, reduced glomerular nephrin immunofluorescence and nephrin protein by immunoblotting, and increased glomerular VEGF immunostaining and renal VEGF protein content. Diabetic animals receiving test compound showed significant lowering of proteinuria, normalization of renal TGF-β1 protein, and significant restoration of altered glomerular nephrin and VEGF expression. Conclusion The findings causally implicate the increased glycated albumin associated with the diabetic state in the abnormal renal nephrin and VEGF expression found in diabetes, thereby promoting proteinuria and glomerulosclerosis. |
| Databáze: | OpenAIRE |
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