Kidney international, 2007-08, Vol.72 (4), p.481-488
2007
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- Autor(en) / Beteiligte
- Titel
- Advanced glycation end products decrease mesangial cell MMP-7: A role in matrix accumulation in diabetic nephropathy?
- Ist Teil von
- Kidney international, 2007-08, Vol.72 (4), p.481-488
- Ort / Verlag
- New York, NY: Elsevier Inc
- Erscheinungsjahr
- 2007
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Increased extracellular matrix material is a pathological hallmark of diabetic nephropathy. In addition to collagens, a variety of non-collagenous glycoproteins such as fibronectin also accumulate in the kidney of diabetics. The effect of diabetes on degradative pathways, in particular those involving non-collagenous proteins, are relatively unexplored. In this study, we determined the expression of the major matrix metalloproteinase (MMP) responsible for degrading the non-collagenous matrix glycoprotein fibronectin. Furthermore, the modulation of these MMPs by advanced glycation end products (AGE), a key factor in the diabetic milieu, was explored. Exposure of mesangial cells to AGEs led to a significant reduction in MMP-7, but not MMP-3 or -10. MMP-7 expression was normalized by both aminoguanidine, an inhibitor of glycation product formation, or by a neutralizing anti-transforming growth factor-β (TGF-β) antibody. In streptozotocin-induced diabetic rats, the diminution in MMP-7 expression and excessive fibronectin accumulation were attenuated by aminoguanidine. Humans with type 2 diabetes and nephropathy displayed similar alterations in MMP-7 to their rodent counterparts. Our findings suggest that diminished expression of the glycoprotein-degrading enzyme, MMP-7, may play a role in fibronectin accumulation in the diabetic kidney in response to AGEs and/or TGF-β.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0085-2538eISSN: 1523-1755DOI: 10.1038/sj.ki.5002357Titel-ID: cdi_proquest_miscellaneous_68145653
- Format
- –
- Schlagworte
- Adult, advanced glycation end product, Animals, Antibodies, Associated diseases and complications, Biological and medical sciences, Cells, Cultured, Culture Media, Conditioned - metabolism, Diabetes Mellitus, Experimental - enzymology, Diabetes Mellitus, Experimental - metabolism, Diabetes Mellitus, Experimental - pathology, Diabetes Mellitus, Type 2 - complications, Diabetes Mellitus, Type 2 - enzymology, Diabetes Mellitus, Type 2 - metabolism, Diabetes Mellitus, Type 2 - pathology, Diabetes. Impaired glucose tolerance, Diabetic Nephropathies - enzymology, Diabetic Nephropathies - etiology, Diabetic Nephropathies - metabolism, Diabetic Nephropathies - pathology, diabetic nephropathy, Down-Regulation, Endocrine pancreas. Apud cells (diseases), Endocrinopathies, extracellular matrix, Female, fibronectin, Fibronectins - genetics, Fibronectins - metabolism, Glycation End Products, Advanced - metabolism, Glycation End Products, Advanced - pharmacology, Glycosylation - drug effects, Guanidines - pharmacology, Humans, Kidneys, Male, Matrix Metalloproteinase 10 - metabolism, Matrix Metalloproteinase 3 - metabolism, Matrix Metalloproteinase 7 - genetics, Matrix Metalloproteinase 7 - metabolism, Medical sciences, mesangial cells, Mesangial Cells - drug effects, Mesangial Cells - enzymology, Mesangial Cells - metabolism, Mesangial Cells - pathology, Middle Aged, Nephrology. Urinary tract diseases, Rats, Rats, Sprague-Dawley, RNA, Messenger - metabolism, Time Factors, Transforming Growth Factor beta - immunology, Transforming Growth Factor beta - metabolism, Urinary system involvement in other diseases. Miscellaneous