Matrix metalloproteinase-2, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 in the peripheral blood of patients with various glomerular diseases and their implication in pathogenetic lesions: study based on an enzyme-linked assay and immunohistochemical staining

Endo, Tetsuro; Nakabayashi, Kimimasa; Sekiuchi, Makiho; Kuroda, Tadahide; Soejima, Akinori; Yamada, Akira

doi:10.1007/s10157-006-0438-3

Cited by 21 publications

(22 citation statements)

References 22 publications

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“…Diabetes affects ECM degradation, and activities of MMPs and TIMPs mostly regulate this process (27). Type IV collagenases, MMP-2 and -9, have been studied extensively in various glomerular diseases with conflicting results (10,14,26,27). However, in the present study, we found that both MMP-2 and -9 activities were increased significantly in diabetic kidney.…”

Section: Glomerular Tissue Levels Of Hcy and Nitric Oxide (No)contrasting

confidence: 42%

Ciglitazone, a PPARγ agonist, ameliorates diabetic nephropathy in part through homocysteine clearance

Sen¹,

Rodríguez²,

Tyagi³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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Sen U, Rodriguez WE, Tyagi N, Kumar M, Kundu S, Tyagi SC. Ciglitazone, a PPAR␥ agonist, ameliorates diabetic nephropathy in part through homocysteine clearance. Am J Physiol Endocrinol Metab 295: E1205-E1212, 2008. First published September 9, 2008 doi:10.1152/ajpendo.90534.2008.-Diabetes and hyperhomocysteinemia (HHcy) are two independent risk factors for glomeruloslerosis and renal insufficiency. Although PPAR␥ agonists such as ciglitazone (CZ) are known to modulate diabetic nephropathy, the role of CZ in diabetes-associated HHcy and renopathy is incompletely defined. We tested the hypothesis that induction of PPAR␥ by CZ decreases tissue Hcy level; this provides a protective role against diabetic nephropathy. C57BL/6J mice were administered alloxan to create diabetes. Mice were grouped to 0, 1, 10, 12, and 16 wk of treatment; only 12-and 16-wk animals received CZ in drinking water after a 10-wk alloxan treatment. In diabetes, PPAR␥ cDNA, mRNA, and protein expression were repressed, whereas an increase in plasma and glomerular Hcy levels was observed. CZ normalized PPAR␥ mRNA and protein expression and glomerular level of Hcy, whereas plasma level of Hcy remained unchanged. GFR was dramatically increased at 1-wk diabetic induction, followed by hypofiltration at 10 wk, and was normalized by CZ treatment. This result corroborated with glomerular and preglomerular arteriole histology. A steady-state increase of RVR in diabetic mice became normal with CZ treatment. CZ ameliorated decrease bioavailability of NO in the diabetic animal. Glomerular MMP-2 and MMP-9 activities as well as TIMP-1 expression were increased robustly in diabetic mice and normalized with CZ treatment. Interestingly, TIMP-4 expression was opposite to that of TIMP-1 in diabetic and CZ-treated groups. These results suggested that diabetic nephropathy exacerbated glomerular tissue level of Hcy, and this caused further deterioration of glomerulus. CZ, however, protected diabetic nephropathy in part by activating PPAR␥ and clearing glomerular tissue Hcy.peroxisome proliferator-activated receptor-␥; matrix metalloproteinase; tissue inhibitor of metalloproteinases; glomerulosclerosis PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-␥ (PPAR␥) is a member of nuclear hormone receptor superfamily of ligandactivated transcription factors. It plays important roles in maintaining glucose and lipid homeostasis (39). The PPAR␥ agonists, such as ciglitazone (CZ), are agents that improve glycemic control by increasing insulin sensitivity (5). These agonists also mediate direct antiatherogenic effects in the diabetic vasculature that are independent of their metabolic actions (4). In the pathogenesis of diabetic vasculopathies, such as in glomerulosclerosis, downregulated PPAR␥ expression is associated with matrix accumulation and glomerulonephritis (23,30,39). Several studies have shown the efficacy of PPAR␥ agonists to ameliorate the progression of glomerulosclerosis (15) and have suggested that PPAR␥ ligands have a direct beneficial renal effect. However, the role...

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Section: Glomerular Tissue Levels Of Hcy and Nitric Oxide (No)contrasting

confidence: 42%

Ciglitazone, a PPARγ agonist, ameliorates diabetic nephropathy in part through homocysteine clearance

Sen¹,

Rodríguez²,

Tyagi³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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“…There is accumulating evidence that MMP-2 is involved in the development and progression of CKD and CVD by eliciting tissue remodeling via structural alterations in the glomerular and tubular areas as well as blood vessels [5,6,7,8]. Further, the plasma MMP-2 level is shown to be positively correlated with serum creatinine (Cr) levels in patients with CKD [9, 10]. In addition, Pawlak et al [11] have demonstrated that plasma MMP-2 but not MMP-9 significantly increased in hemodialysis patients and correlated with intima media thickness (IMT) levels.…”

Section: Introductionmentioning

confidence: 99%

Circulating Matrix Metalloproteinase-2 Is an Independent Correlate of Proteinuria in Patients with Chronic Kidney Disease

et al. 2008

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Background/Aim:Matrix metalloproteinase-2 (MMP-2) has been implicated in chronic kidney disease (CKD) and cardiovascular disease. However, there is no knowledge about the correlations between serum levels of MMP-2, proteinuria and atherosclerosis in patients with CKD. We investigated whether serum MMP-2 levels were associated with proteinuria, intima media thickness (IMT), and the presence of carotid atherosclerotic plaque in CKD patients. Methods: CKD patients without hemodialysis (n = 99) were enrolled. MMP-2 levels were measured by an ELISA system. IMT and carotid atherosclerotic plaque were evaluated by a high-resolution ultrasonography. Results: Multivariate analyses revealed that low-density lipoprotein (p < 0.001), MMP-2 (p = 0.001) and systolic blood pressure (p = 0.011) were independent correlates of proteinuria. Age- and serum creatinine-adjusted MMP-2 levels were significantly increased (p = 0.001) in proportion to the increasing levels of proteinuria. Further, age (p < 0.001), systolic blood pressure (p = 0.015) and MMP-2 levels (p = 0.042) were independent correlates of IMT. MMP-2 levels were significantly (p < 0.01) higher in patients with atherosclerotic plaque than those without it. Conclusions: The present study demonstrated that serum levels of MMP-2 were one of the independent correlates of proteinuria and IMT in patients with CKD. Our results suggest that serum MMP-2 levels may be one of the risk factors for renal damage and atherosclerosis in CKD patients.

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“…[15,25] Many factors and markers can affect collagen remodeling in the glomerular basement membrane, including gelatinases and their inhibitory protein TIMP. [12][13][14]16,26] Elevated levels of biomarkers associated with matrix regulation in UTI were reported recently. Hatipoglu et al [27] measured the ratio of MMP9 to NGAL to Cr in children with symptomatic UTI, and compared them with asymptomatic patients with a contaminated urine exam, as well as with healthy children.…”

Section: Discussionmentioning

confidence: 99%

“…Of these, the gelatinases (MMP2 and MMP9), in particular, have specific activity on type IV collagen, which is the main constituent of matrix. [15,16] The degradation of ECM is restrained by tissue inhibitors of metalloproteinases (TIMPs), which inhibit MMPs. Disruption of the balance between MMPs and their inhibitors may lead to fibrinogenesis and scar formation in the kidney.…”

Section: Introductionmentioning

confidence: 99%

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Urinary matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 biomarkers for predicting renal scar in children with urinary tract infection

Abedi

Mohammadjafari

Rafiei

et al. 2017

Turkish Journal of Urology

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Objective: Urinary tract infection occurs in 1.8-6.6% of children under 6 years old. The aim of this study was to assess the urinary concentrations of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1), in children with acute pyelonephritis (APN) and the potential to develop renal scarring. Material and methods:Children who had experienced an episode of APN were divided into 2 groups. Group 1 included children with APN who exhibited scarring and group 2 included children with APN who had a normal 99m Technetium dimercaptosuccinic acid scan. Urinary levels of MMP9 and TIMP1 were measured in the acute phase of infection. A receiver operating characteristic curve was generated to allow calculation of cut-off values.Results: Sixty-one children were enrolled across the 2 groups: group 1 contained 16 patients (all female); group 2, 38 children (36 female and 2 male). Urinary levels of MMP9 and TIMP1 were significantly higher in group 1 than in group 2 (p= 0.037 and 0.022 respectively). For comparison of groups 1 and 2, the cut-off values were measured as 75.5 ng/mL (sensitivity 62.5%, specificity 71.1%, positive predictive value, PPV, 48%, negative predictive value, NPV, 82%), 16.1 ng/mL (sensitivity 75%, specificity 55.3%, PPV 41%, NPV 84%), and 1310.7 ng/mL (sensitivity 75% specificity 60.5%, PPV 44%, NPV 85%) for MMP9, TIMP1, and MMP9×TIMP1 levels, respectively. Conclusion:Evaluation of urinary MMP9 and TIMP1 levels may help to identify children with APN who are at risk of developing renal scarring.Keywords: Children; matrix metalloproteinase; pyelonephritis; tissue inhibitor of metalloproteinase 1; urinary tract infection; vesico-ureteral reflux.Cite this article as: Abedi SM, Mohammadjafari H, Rafiei A, Bazi S, Yazdani P. Urinary matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 biomarkers for predicting renal scar in children with urinary tract infection. Turk J Urol 2017; 43(4): 536-42.

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Matrix metalloproteinase-2, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 in the peripheral blood of patients with various glomerular diseases and their implication in pathogenetic lesions: study based on an enzyme-linked assay and immunohistochemical staining

Abstract: These results therefore suggest that MMP-2 plays an important role in the degradation of GBM, while MMP-9 only moderately affects the degradation of MM.

Cited by 21 publications

References 22 publications

Ciglitazone, a PPARγ agonist, ameliorates diabetic nephropathy in part through homocysteine clearance

Ciglitazone, a PPARγ agonist, ameliorates diabetic nephropathy in part through homocysteine clearance

Circulating Matrix Metalloproteinase-2 Is an Independent Correlate of Proteinuria in Patients with Chronic Kidney Disease

Urinary matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 biomarkers for predicting renal scar in children with urinary tract infection

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