Gene/Protein Disease Symptom Drug Enzyme Compound
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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.
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PMID:Localization of glycated proteins in the glomeruli of patients with diabetic nephropathy. 904 11

One of the major causes of glomerular sclerosis which precedes renal failure is an increase in glomerular extracellular matrices (ECMs). Glomerular ECMs which are composed of mesangial matrix and basement membrane play an important role in physical, mechanical and structural functions of the glomerulus. Matrix metalloproteinases (MMPs) are the enzymes which degrade both the collagenous and noncollagenous components of the ECMs. Tissue inhibitors of metalloproteinases (TIMPs) are inhibitors of MMPs. The regulations by MMPs and TIMPs are considered to contribute to maintain homeostasis in the production and degradation of ECMs in the glomeruli. In the glomeruli of patients with glomerulonephritis, the imbalance between production and degradation of ECMs is supposed to cause the increase in ECMs and glomerular sclerosis. In this study, serum concentrations of MMP-1, -2, and -3, TIMP-1 and 2 and type IV collagen were measured in patients with IgA nephropathy, lupus nephritis and membranous nephropathy. In patients with IgA nephropathy and lupus nephritis which are mesangial proliferative glomerulonephritis, the levels of MMP-3 and TIMP-2 were increased. On the other hand, the levels of type IV collagen, MMP-2 and TIMP-1 were increased in patients with membranous nephropathy in which the thickening of basement membrane is characteristic. These differences may be caused by the difference of the pathogenesis of these diseases. The present results suggest that the imbalance between the metabolism of ECMs occurs in patients with glomerulonephritis and contributes to the progression of glomerulonephritis.
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PMID:Changes in serum concentrations of matrix metalloproteinases, tissue inhibitors of metalloproteinases and type IV collagen in patients with various types of glomerulonephritis. 909 Jul 49

In IgA nephropathy (IgAN), IgA immune complexes are deposited in the mesangium and drive inflammation and extracellular matrix (ECM) remodelling. The functional links between IgA deposition, inflammation, and matrix remodelling are not well characterized. We recently performed urine liquid chromatography-tandem mass spectrometry proteomics and identified multiple ECM glycoproteins whose expression and function in IgAN is unclear. None of the urine glycoproteins was regulated in IgAN transcriptomics, indicating that tissue remodelling rather than increased expression might contribute to their presence in urine. To investigate this, we examined the IgAN expression profile of metalloproteinases, enzymes involved in the remodelling of ECM proteins, and noted that the proteoglycanase ADAMTS5 was upregulated in IgAN kidneys. ADAMTS5 accumulated in areas of inflammation, and ADAMTS5+ cells were seen in the tubulointerstitium and glomeruli. The enzyme was expressed by CD64+ cells and its expression was increased by IL-1 and LPS. Analysis of myeloid cell transcriptomics revealed that ADAMTS5 is enriched in human classical monocytes. ADAMTS5+ cells were present in areas of matrix remodelling and associated with ECM proteins lumican, versican, and collagen-4. Liquid chromatography-tandem mass spectrometry proteomics of kidney explants digested with ADAMTS5, identified multiple kidney proteins affected by ADAMTS5 and revealed specific proteolysis of complement C3 and fibronectin associated with IgA on immune complexes. ADAMTS5 processing of immune complex proteins reduced binding to cultured mesangial cells. ADAMTS5 is associated with interstitial inflammatory cells in IgAN and other kidney lesions and fragments relevant extracellular proteins. The proteolytic enzyme might be a new translational target relevant to inflammation and scarring in kidney disease.
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PMID:The Metalloproteinase ADAMTS5 Is Expressed by Interstitial Inflammatory Cells in IgA Nephropathy and Is Proteolytically Active on the Kidney Matrix. 3291 86