Matrix Metalloproteinase-2 Dysregulation in Type 1 Diabetes

Thrailkill, Kathryn M.; Bunn, R. Clay; Moreau, Cynthia; Cockrell, Gael; Simpson, Pippa; Coleman, Hannah N.; Frindik, J. Paul; Kemp, Stephen F.; Fowlkes, John L.

doi:10.2337/dc07-0162

Cited by 102 publications

(103 citation statements)

References 31 publications

(24 reference statements)

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“…Furthermore, in vitro studies using rat artery samples demonstrated that endothelial cells express MMP mRNA during hyperglycemia [38]. Consistently elevated plasma levels of MMP-2 were found in type I and type 2 diabetic patients when compared to nondiabetic controls [39, 40]. Therefore, it seems likely that the risk factor profile may account for differences in MMP expression before and after acute stroke.…”

Section: Discussionmentioning

confidence: 99%

Single-Nucleotide Polymorphisms of MMP-2 Gene in Stroke Subtypes

et al. 2008

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Background: Matrix metalloproteinases (MMP) are expressed after ischemic stroke. These proteases are responsible for a higher incidence of hemorrhages, are correlated to size of infarction and influence the effects of recombinant tissue plasminogen activator treatment. We therefore evaluated single nucleotide polymorphisms (SNP) of MMP-2 in different subtypes of stroke patients in an association study using a case-control design. Methods: 197 stroke patients were divided according to modified TOAST criteria (small vessel disease, large vessel disease, hemorrhagic stroke and asymptomatic carotid artery stenosis) and compared to 143 controls. Clinical data like age, sex, risk factors and diagnostic results including MRI or cranial CT scans and ultrasound evaluations of intra- and extracranial arteries were obtained. Genotypes of MMP-2 (12 SNP) were compared to controls and DNA samples were analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis. Logistic regression analysis was performed for small vessel disease to test for interactions between markers and defined clinical risk factors. Additionally, MMP-2 serum levels obtained in the first 24 h after stroke were measured. Results: From the MMP-2 gene, 5 markers (rs1030868, rs2241145, rs2287074, rs2287076, rs7201) showed a significant association with small vessel infarcts (p < 0.05) and rs7201:g.C was identified as an independent risk factor by multivariable logistic regression analysis. MMP-2 protein levels were significantly lower in this group (174 ± 48 ng/dl) versus controls (214 ± 56 ng/dl). For other stroke subtypes, no significant association with MMP-2 SNP could be found. Conclusion: Our study demonstrates an association of the MMP-2 gene with the development of lacunar stroke, and no association of MMP-2 with other stroke subtypes.

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Section: Discussionmentioning

confidence: 99%

Single-Nucleotide Polymorphisms of MMP-2 Gene in Stroke Subtypes

et al. 2008

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“…Urine has been analyzed to identify disease biomarkers for diseases including coronary artery disease [6], renal cell carcinoma [7], prostate cancer [8,9], diabetes [10], and renal diseases [11][12][13][14][15][16]. The analysis of naturally occurring small molecular weight (MW) endogenous peptide analysis is termed as "peptidomics."…”

Section: Introductionmentioning

confidence: 99%

Urinary Peptidomic Analysis Identifies Potential Biomarkers for Acute Rejection of Renal Transplantation

et al. 2009

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Introduction Human urine is a complex matrix of proteins, endogenous peptides, lipids, and metabolites. The level of any or all of these components can reflect the pathophysiological status of an individual especially of the kidney at the time of urine collection. The naturally occurring endogenous urinary peptides which are thought to be the product of several proteolytic and degradation processes may provide clinically useful biomarkers for different renal and systemic diseases. Materials and MethodsTo examine if specific differences in the urinary peptidome (<10 kDa) occur at the time of acute renal transplant rejection (AR), we undertook a study of urine samples collected from biopsy-proven AR (n=10), stable graft function (n=10), and healthy normal control (n=10). The peptides (<10 kDa) were extracted and fractionated with high-performance liquid chromatography followed by matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometric (MS) analysis. Results We identified 54 endogenous peptides, including multiple peptides for Tamm-Horsfall protein (UMOD). A panel of peptides are identified which discriminate renal transplant patients with AR from stable graft. We have shown that liquid chromatography followed by MALDI is a useful tool to identify potential biomarkers, which after verification with larger patient cohort can be used as a noninvasive monitoring tool for renal transplant rejection.

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“…An elevation in urinary MMP-2 levels and MMP-2 enzyme activity has also been observed in type 1 DM patients with albuminuria, in comparison to nonalbuminuric diabetic patients or control subjects [163, 164]. In addition, podocytes were detected in the urinary sediment of albuminuric diabetic patients, but not in patients with type 1 DM without albuminuria or control subjects [165].…”

Section: Gelatinases (Mmp-2 Mmp-9)mentioning

confidence: 99%

Matrix Metalloproteinases in Renal Diseases: A Critical Appraisal

Zakiyanov

Kalousová

Zima

et al. 2019

Kidney Blood Press Res

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Matrix metalloproteinases (MMPs) are endopeptidases within the metzincin protein family that not only cleave extracellular matrix (ECM) components, but also process the non-ECM molecules, including various growth factors and their binding proteins. MMPs participate in cell to ECM interactions, and MMPs are known to be involved in cell proliferation mechanisms and most probably apoptosis. These proteinases are grouped into six classes: collagenases, gelatinases, stromelysins, matrilysins, membrane type MMPs, and other MMPs. Various mechanisms regulate the activity of MMPs, inhibition by tissue inhibitors of metalloproteinases being the most important. In the kidney, intrinsic glomerular cells and tubular epithelial cells synthesize several MMPs. The measurement of circulating MMPs can provide valuable information in patients with kidney diseases. They play an important role in many renal diseases, both acute and chronic. This review attempts to summarize the current knowledge of MMPs in the kidney and discusses recent data from patient and animal studies with reference to specific diseases. A better understanding of the MMPs’ role in renal remodeling may open the way to new interventions favoring deleterious renal changes in a number of kidney diseases.

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Matrix Metalloproteinase-2 Dysregulation in Type 1 Diabetes

Cited by 102 publications

References 31 publications

Single-Nucleotide Polymorphisms of MMP-2 Gene in Stroke Subtypes

Single-Nucleotide Polymorphisms of MMP-2 Gene in Stroke Subtypes

Urinary Peptidomic Analysis Identifies Potential Biomarkers for Acute Rejection of Renal Transplantation

Matrix Metalloproteinases in Renal Diseases: A Critical Appraisal

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