Inhibiting albumin glycation attenuates dysregulation of VEGFR-1 and collagen IV subchain production and the development of renal insufficiency
| Autor: | Margo P. Cohen, Amy Wang, Sheldon Chen, Gregory T. Lautenslager, Elizabeth Shea, Elizabeth Hud, Clyde W. Shearman |
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| Rok vydání: | 2006 |
| Předmět: |
Collagen Type IV
Male medicine.medical_specialty Diclofenac Glycosylation Physiology Urinary system Mice Obese urologic and male genital diseases Kidney Diabetes Mellitus Experimental Mice Glycation Internal medicine Diabetes mellitus Amadori rearrangement Albumins medicine Animals Renal Insufficiency Protein kinase A chemistry.chemical_classification Vascular Endothelial Growth Factor Receptor-1 Albumin Membrane Proteins medicine.disease Endocrinology chemistry Creatinine Glycoprotein Kidney disease |
| Zdroj: | American journal of physiology. Renal physiology. 292(2) |
| ISSN: | 1931-857X |
| Popis: | Glomerular cells in culture respond to albumin containing Amadori glucose adducts (the principal serum glycated protein), with activation of protein kinase C-β1, increased expression of transforming growth factor (TGF)-β1, the TGF-β type II signaling receptor, and the extracellular matrix proteins α1(IV) collagen and fibronectin and with decreased production of the podocyte protein nephrin. Decreasing the burden of glycated albumin in diabetic db/db mice significantly reduces glomerular overexpression of TGF-β1 mRNA, restores glomerular nephrin immunofluorescence, and lessens proteinuria, mesangial expansion, renal extracellular matrix protein production, and increased glomerular vascular endothelial growth factor (VEGF) immunostaining. In the present study, db/db mice were treated with a small molecule, designated 23CPPA, that inhibits the nonenzymatic condensation of glucose with the albumin protein to evaluate whether increased glycated albumin influences the production of VEGF receptors (VEGFRs) and type IV collagen subchains and ameliorates the development of renal insufficiency. Renal levels of VEGF and VEGFR-1 proteins and serum creatinine concentrations were significantly higher and renal levels of α3(IV) collagen and nephrin proteins and endogenous creatinine clearance values were significantly lower in control diabetic than in age-matched nondiabetic ( db/m) mice. These changes were significantly attenuated in db/db littermate mice treated from 9 to 18 wk of age with 23CPPA. The findings indicate that inhibiting excess nonenzymatic glycation of serum albumin improves renal molecular biology abnormalities and protects against the development of renal insufficiency in the db/db mouse. |
| Databáze: | OpenAIRE |
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