Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycation of proteins is regarded as one of the major causes of the development and progression of diabetic nephropathy. Based on the numerous reports on experimental models and on our own newly developed techniques, we planned to localize Amadori products and advanced glycation end-products (AGEs), as well as the mRNA expression of cytokines, enzymes and their inhibitors, which are responsible for the expansion of the mesangial areas of the glomeruli. Ten patients with diabetic nephropathy were examined. Patients with immunoglobulin (Ig) A nephropathy and normal portions of the surgically removed kidneys served as controls. Amadori products and AGEs in biopsy specimens were stained by specific monoclonal antibodies, and mRNA expression of the above substances was detected by in situ hybridization. There was a parallel progression in the degree of staining with anti-Amadori product antibody or anti-AGE antibody with the severity of tissue damage in patients with diabetic nephropathy. Patients with IgA nephropathy and normal renal tissues did not show any positive staining with these antibodies. The expression of transforming growth factor beta 1, stromelysin and tissue inhibitor of matrix proteinase 1 in the glomeruli was decreased in diabetic patients with advanced tissue damage, but they were progressively expressed in the advanced stage of IgA nephropathy. It is concluded that Amadori products and of AGEs were formed in parallel in diabetic kidneys. The decrease in the expression of the cytokine and enzymes might be due to altered protein formation associated with glycation.
Nephrol Dial Transplant 1996
PMID:Localization of glycated proteins in the glomeruli of patients with diabetic nephropathy. 904 11

Mesangial cells are responsible for the synthesis of mesangial matrix as well as its degradation, which is mediated by a number of proteolytic activities, including metalloproteinases (MMPs). Imbalanced matrix protein metabolism may be responsible for mesangial expansion and glomerulosclerosis in diabetic nephropathy. Heparin prevents this complication. In human and murine mesangial cell cultures, RT-PCR was able to detect mRNA expression for a number of molecules involved in the mesangial extracellular matrix turnover: type IV collagen [alpha 1(IV)COLL], MMP-1, MMP-2, MMP-3, MMP-9 and MMP-10, and the tissue inhibitors TIMP-1 and TIMP-2. The expression of mRNA for alpha 1(IV)COLL and MMP-2/TIMP-2 balance was studied in human cells in the presence of high glucose and heparin. mRNAs for all the studied molecules were expressed at different levels. Interestingly, a shift in the balance of alpha 1(IV)COLL, MMP-2 and TIMP-2 was observed in high glucose, which was partially reversed by heparin supplementation. The new equilibrium was mostly due to the down-regulation of type IV collagen expression, rather than further reduction of potential proteolysis. Our data, while extending the list of potential mediators of mesangial matrix catabolism, highlight a molecular mechanism by which the pathogenesis of diabetic nephropathy may be sustained, and at the same time suggest that heparin may have the potential to correct this abnormality.
Nephrol Dial Transplant 1997 Mar
PMID:Effect of glucose and heparin on mesangial alpha 1(IV)COLL and MMP-2/TIMP-2 mRNA expression. 907 22