Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined metalloproteinase (MMP)-1, -2, -3, and -9 mRNA expression by peripheral blood monocytes from 50 patients with immunoglobulin A (IgA) nephropathy, 20 with membranous nephropathy, 10 with minimal-change nephrotic syndrome, five with focal glomerulosclerosis, 30 with non-IgA proliferative glomerulonephritis, and 40 healthy normal controls who were comparable with regard to age and sex. Monocytes from patients with IgA nephropathy expressed a higher level of MMP-9 mRNA than those from patients with other forms of glomerulonephritis or from healthy controls (MMP-9 to glyceraldehyde-3-phosphate dehydrogenase ratio: IgA nephropathy, 1.68 +/- 0.24; membranous nephropathy, 0.22 +/- 0.08; minimal-change nephrotic syndrome, 0.24 +/- 0.06; focal glomerulosclerosis, 0.32 +/- 0.08; non-IgA proliferative glomerulonephritis, 0.30 +/- 0.12; and healthy controls, 0.16 +/- 0.04). When the biopsy specimens were classified into four grades according to the severity of glomerular and interstitial pathology, highly significant differences were observed among MMP-9 mRNA levels in monocytes from all four groups of patients with IgA nephropathy (grade I, 0.44 +/- 0.09; grade II, 1.06 +/- 0.26; grade III, 2.22 +/- 0.68; grade IV, 2.86 +/- 0.88). In addition, MMP-9 mRNA levels from patients with IgA nephropathy correlated with urinary protein excretion (P < 0.001). However, we detected minimal mRNA expression of MMP-1, -2, and -3 by peripheral blood monocytes from patients with IgA nephropathy or other forms of glomerulonephritis and from normal healthy controls. Our results suggest that increased MMP-9 mRNA expression in circulating monocytes may contribute to the progression of IgA nephropathy.
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PMID:Increased mRNA expression of metalloproteinase-9 in peripheral blood monocytes from patients with immunoglobulin A nephropathy. 871 19

In 30% cases nephrotic syndrome is due to membranous glomerulonephritis (MG). Fifty percent of patients reveal end stage renal disease in 15 years follow-up. The another 50% gain persistent remission. The pathogenesis of disease is not known. Protein accumulation in glomeruli leads to progressive loss of kidney structure and function in MG. Also the role of tissue proteolytic systems and growth factors in this process is not known. We aimed to estimate urine cathepsin B, collagenase activity and urine excretion of TGF-beta 1 and fibronectin in MG. MG patients revealed increased urine cathepsin B activity (10.58 +/- 8.73 pmol AMC/mg creatinine/min. vs. control 7.11 +/- 2.05 pmol AMC/mg creatinine/min. [p < 0.05]), urine collagenase activity (8.59 +/- 4.26 pmol AMC/mg creatinine/min. vs. control 3.84 +/- 2.09 pmol AMC/mg creatinine/min. [p > 0.02]) and increased urine excretion of fibronectin (214 +/- 335 ng/mg creatinine vs. control 12.7 +/- 6.7 ng/mg creatinine [p < 0.05]) and increased urine excretion of TGF-beta 1 (283.55 +/- 248.13 pg/ml vs. control 36.11 +/- 48.01 pg/ml [p < 0.05]). The results indicates on glomerular overproduction of TGF-beta 1 and urinary leak of proteolytic enzymes which may exacerbate glomerular proteolytic activity in MG. This may lead to glomerular protein accumulation and progressive loss of kidney function and structure in MG. Increased urine fibronectin excretion in MG patients seems to confirm the hypothesis.
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PMID:[Activity of cathepsin B and collagenase in urine and excretion of fibronectin and TGF-beta 1 in urine of patients with membranous glomerulonephritis]. 955 72

In 30% of cases nephrotic syndrome is caused by membranous glomerulonephritis (MG). Protein accumulation in glomeruli leads to progressive loss of kidney function and damage of structure in MG. The role of tissue proteolytic systems and growth factors in this process is not known. The purpose of the study was to estimate urine cathepsin B, collagenase activity and urine excretion of TGF-beta 1 and fibronectin in MG. Cathepsin B activity was greater in the urine of MG patients than in the control group (10.58 +/- 8.73 pmol AMC/mg creatinine per min-1 vs control 7.11 +/- 2.05 pmol AMC/mg creatinine per min-1; P < 0.05). Urine collagenase activity was higher in the group of patients than in the control group (8.59 +/- 4.26 pmol AMC/mg creatinine per min-1 vs control 3.84 +/- 2.09 pmol AMC/mg creatinine per min-1 P < 0.02). Urine excretion of fibronectin (45.60 ng/mg creatinine vs control 10.30 ng/mg creatinine; P < 0.04) and TGF-beta 1 levels in the urine were higher than in controls (283.55 +/- 248.13 pg/ml vs 36.11 +/- 48.01 pg/ml; P < 0.01). Results suggest glomerular overproduction of TGF-beta 1 and urinary leak of proteolytic enzymes (PE). This may result in decreased glomerular PE activity in MG and, with time, may lead to protein accumulation in renal glomeruli and to progressive loss of kidney function and damage of structures as the course of MG progresses. PE urine composition as well as ECM protein and cytokine urine excretion may allow noninvasive glomerulopathy course monitoring in humans in the future.
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PMID:Urine activity of cathepsin B, collagenase and urine excretion of TGF-beta 1 and fibronectin in membranous glomerulonephritis. 987 98

Abnormalities of extracellular matrix (ECM) metabolism, i.e., overproduction and/or inhibition of ECM breakdown, may contribute to progression of fibrotic degeneration in the kidney. Earlier studies revealed that major ECM components, type I, III, and IV collagens, etc., were accumulated in glomeruli and tubulointerstitium in kidneys of Institute of Cancer Research (ICR) derived glomerulonephritis (ICGN) mice which are a novel inbred strain of mice with a hereditary nephrotic syndrome of unknown etiology and are considered to be a good model of human idiopathic nephrotic syndrome. In the present study, we compared the activities of matrix metalloproteinases (MMPs), a family of enzymes that degrade ECM components, in the kidneys of aged ICGN mice and age-matched ICR mice as normal controls. We biochemically measured interstitial collagenase (MMP-1), gelatinase (MMP-2 and MMP-9), and stromelysin (MMP-3) activities in the kidney tissues. Lower activities of MMP-1 and MMP-2 and MMP-9 were demonstrated in the kidneys of ICGN mice as compared with those of ICR mice, but there were no significant differences in the MMP-3 activities between these strains. These results show that decreased MMP activities cause abnormal accumulation of ECM in ICGN mouse kidneys.
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PMID:Decreased matrix metalloproteinase activity in the kidneys of hereditary nephrotic mice (ICGN strain). 1101 84

Diabetic nephropathy (DN) characterized as nephrotic syndrome and diffuse glomerulosclerosis can cause renal failure and end-stage kidney disease. Expansion of mesangial matrix around capillaries in the kidney glomeruli is a prominent feature of DN. This study investigated whether licorice extracts inhibited mesangial cell (MC) proliferation and matrix accumulation induced by high glucose (HG). Human renal MC were cultured in media containing 5.5 mM glucose plus 27.5 mM mannitol as an osmotic control or 33 mM glucose for 3 d in the presence of water or ethanol extracts from raw licorice (LW, LE) or roasted licorice (RLW, RLE). Non-polar components including glycyrrhetic acid were elevated during licorice roasting, whereas polar components soluble in water extracts were diminished. Exposure of cells to HG caused significant increases in collagen IV secretion and connective tissue growth factor (CTGF) expression, which was appeased by RLW and RLE at transcriptional levels. The inhibitory potency was high in the order of RLE > or = RLW > or = LE > > LW. Non-polar glycyrrhetic acid but not glycyrrhizin retarded HG-stimulated mesangial matrix deposition through diminishing CTGF expression. In addition, RLW and RLE but not LW modulated membrane type matrix metalloproteinase-1 (MT-1 MMP) expression, MMP-2 activity and tissue inhibitor of MMP-2 (TIMP-2), which facilitated the degradation of mesangial matrix. Furthermore, the augmented expression of CTGF and TIMP-2 in HG-exposed cells was mediated by Akt activation and TGF-beta/Smad signaling through PKCbeta2-responsive signaling pathways. However, HG-down-regulated MT-1 MMP expression was independent of activation of ERK1/2 and Akt when using their inhibitors of DB98059 (ERK1/2) and LY294002 (Akt) alone or in combination. These results demonstrate that extracts from roasted licorice may be highly potent therapeutic agents for the prevention and treatment of mesangial fibrosis and glomerulosclerosis leading to diabetes nephropathy due to longstanding diabetes mellitus.
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PMID:Roasted licorice extracts dampen high glucose-induced mesangial hyperplasia and matrix deposition through blocking Akt activation and TGF-beta signaling. 2038 13

In chronic glomerulopathies, renal fibrosis (RF) results from extracellular matrix remodeling processes regulated by matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP). We assessed urinary (u-) and serum (s-) MMP-1, -2, -9, TIMP-1, -2 concentrations and MMP-1, -2, -9/TIMP-1, -2 ratios in children with nephrotic syndrome. Steroid-dependent and steroid-resistant nephrotic patients (SDNS-Ps and SRNS-Ps, respectively) were compared with respect to measured parameters. The correlations of measured parameters with magnitude of proteinuria and histopathological diagnosis were determined.The study comprised of 39 children with nephrotic syndrome and 20 healthy controls. Twenty-three patients had SDNS and 16 ones-SRNS. The concentrations MMPs and TIMPs were measured using enzyme-linked immunosorbent assay.In nephrotic patients, higher u-MMP-1, -2, -9/creatinine ratios and u-TIMP-1, -2/creatinine ratios were observed as compared with controls. Nephrotic children were also characterized by lower MMP-1, -2, -9/TIMP-1 ratios. In SRNS-Ps, u-MMP-2/creatinine ratio and u-TIMP-1/creatinine ratio were higher as compared with SDNS-Ps. Magnitude of proteinuria correlated positively with u-MMP-2/creatinine ratio and negatively with u-MMP-2/TIMP-1. In minimal change disease (MCD) patients as compared with those with other glomerulopathies, there was higher u-MMP-2/TIMP-1 ratio. No significant differences in s-MMPs, s-TIMPs, and s-MMPs/TIMPs ratios between nephrotic patients and controls were observed.Children with nephrotic syndrome are characterized by increased u-fibrotic biomarkers excretions. U-MMP-1, -2, -9 excretions and u-MMP-2/TIMP-1 ratio may become potential early biomarkers for RF. SRNS-Ps, those with heavier proteinuria and other than MCD glomerulopathies, seem to be more susceptible to early RF.
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PMID:Urinary metalloproteinases and tissue inhibitors of metalloproteinases as potential early biomarkers for renal fibrosis in children with nephrotic syndrome. 2946 92