Elevation of serum and urine levels of TIMP-1 and tenascin in patients with renal disease

Hörstrup, Jan; Gehrmann, Mathias; Schneider, B.; Plöger, Angela; Froese, P.; Schirop, Th.; Kampf, D; Frei, Ulrich; Neumann, Rainer; Eckardt, Kai‐Uwe

doi:10.1093/ndt/17.6.1005

Cited by 78 publications

(50 citation statements)

References 31 publications

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“…Urinary levels of TIMP-1 were increased in patients with CKD (n ϭ 54) vs. controls (n ϭ 176) (36). The expression of MMP-13 and -14 is elevated in chronic renal inflammation and/or fibrosis in the human kidney (32).…”

Section: Mmps In Chronic Kidney Diseasementioning

confidence: 96%

Role of matrix metalloproteinases in renal pathophysiologies

Catania¹,

Chen²,

Parrish³

2007

American Journal of Physiology-Renal Physiology

345

314

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Matrix metalloproteinases (MMPs) are a large family of proteinases that remodel extracellular matrix (ECM) components and cleave a number of cell surface proteins. MMP activity is regulated via a number of mechanisms, including inhibition by tissue inhibitors of metalloproteinases (TIMPs). Originally thought to cleave only ECM proteins, MMP substrates are now known to include signaling molecules (growth factor receptors) and cell adhesion molecules. Recent data suggest a role for MMPs in a number of renal pathophysiologies, both acute and chronic. This review will focus on the expression and localization of MMPs and TIMPs in the kidney, as well as summarizing the current information linking these proteins to acute kidney injury, glomerulosclerosis/tubulointerstitial fibrosis, chronic allograft nephropathy, diabetic nephropathy, polycystic kidney disease, and renal cell carcinoma.acute kidney injury; chronic allograft nephropathy; diabetic nephropathy; glomerulosclerosis; MMP; polycystic kidney disease; tissue inhibitor of metalloproteinase; tubulointerstitial fibrosis; renal cell carcinoma MATRIX METALLOPROTEINASES (MMPs) are zinc-containing endopeptidases that are involved in remodeling the extracellular matrix (ECM) and are crucial for tissue development and homeostasis. All MMPs are multidomain enzymes, generally consisting of a prodomain, a catalytic domain, a hinge region, and a hemopexin-like domain. Most MMPs are secreted as proMMPs; activation usually requires cleavage of the prodomain by plasmin or other MMPs (88). The propeptide sequence contains a conserved cysteine switch (PRCGXPD) to stabilize and inhibit the catalytic zinc ion, which is bound in a conserved HEXGHXXGXXH motif (53). The hemopexin-like domain is characterized by a "propeller" of four twisted ␤-sheets, which are thought to confer substrate recognition (53). Together, the hinge region and the hemopexin-like domain unravel substrate proteins for subsequent degradation. Originally thought to cleave only ECM proteins, this family of enzymes is now known to cleave a number of non-ECM substrates as well. For example, cell adhesion molecules (cadherins and integrins) and both growth factors and their receptors (TGF-␤, FGF-R1) are targeted by MMPs (74).Tissue inhibitors of metalloproteinases (TIMPs) are endogenous, specific inhibitors that bind and inhibit MMPs. Four TIMPs (TIMP-1-4) have been identified in vertebrates; these proteins share a similar structure which fits into the active site of the MMP catalytic domain. TIMPs inhibit all MMPs, except TIMP-1, which does not inhibit . A number of other MMP inhibitors have been identified, including RECK (81), ␣2-macroglobulin (4), and tissue factor pathway inhibitor-2 (33).MMPs are classified into six groups based on substrate and sequence homology: collagenases, gelatinases, stromelysins, matrilysins, membrane-type matrix metalloproteinases and "other MMPs" (Fig. 1). Collagenases [MMP-1, -8 (neutrophil collagenase), -13, and -18 (Xenopus laevis collagenase)] cleave collagens I, II, and III at a...

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Section: Mmps In Chronic Kidney Diseasementioning

confidence: 96%

Role of matrix metalloproteinases in renal pathophysiologies

Catania¹,

Chen²,

Parrish³

2007

American Journal of Physiology-Renal Physiology

345

314

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“…Timp1 is a glycoprotein expressed in several tissues that acts as an inhibitor of matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. Timp1 is produced by interstitial cells in the kidney and plays a major role in the inhibition of matrix degradation (Chromek et al, 2004;Hörstrup et al, 2002). Spp1 is a matrix glycoprotein containing an arginine-glycine-aspartate motif that binds to the integrin family of receptors and a soluble cytokine.…”

Section: A2mmentioning

confidence: 99%

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

et al. 2012

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-The present study aimed to establish candidate biomarker genes for the early detection of nephrotoxicity in mice, with a particular focus on nephrotoxicity caused by polyene macrolides. Comprehensive gene expression changes were evaluated using microarrays in a mouse model in which acute nephrotoxicity was induced by amphotericin B deoxycholate, trade name Fungizone. The upregulated genes identified through microarray analysis of kidney tissue of Fungizone-treated mice included several genes that have been reported as nephrotoxicity biomarkers in rats, and 14 genes were selected as candidate nephrotoxicity biomarkers. The usefulness of these genes as nephrotoxicity biomarkers in mice was evaluated further through expression profiling under several experimental conditions using real time RT-PCR. Expression of genes encoding kidney injury molecule 1, lipocalin 2, tissue inhibitor of metalloproteinase 1, and secreted phosphoprotein 1 was highly upregulated by Fungizone, nystatin, natamycin, amphotericin B methyl ester, and liposomal amphotericin B, and their area under the ROC curve values were more than 0.95. These genes were more sensitive at detecting nephrotoxicity than traditional clinical chemistry and histopathology parameters. This study provides novel evidence that these nephrotoxicity biomarker genes identified are translatable to mice, and that they are useful for early and sensitive detection of nephrotoxicity.

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“…In studies on potential biomarkers for the detection of AKI, tubular enzymuria, (11)(12)(13) NGAL, (14)(15)(16) KIM-1 (17) and IL-18 (18) were normalised to uCr to control for variations in urinary flow rates. Normalisation is also commonly used in studies regarding CKD or progression of kidney disease, such as studies involving tissue inhibitor of metalloproteinase 1, (19) L-FABP, (20,21) NGAL, (22) N-acetyl-β-D-glucosaminidase and KIM-1.…”

Section: Introductionmentioning

confidence: 99%

Normalisation of urinary biomarkers to creatinine for clinical practice and research – when and why

Tang¹,

Toh²,

Teo³

2015

smedj

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Acute kidney injury (AKI) and chronic kidney disease (CKD) are major health problems. Urinary biomarkers have both diagnostic and prognostic utility in AKI and CKD. However, how biomarker excretion rates should be reported, especially whether they should be normalised to urinary creatinine concentration (uCr), is controversial. Some studies suggest that normalisation to uCr may be inappropriate at times, as urinary creatinine excretion rate may vary greatly, depending on the situation. Notably, recent studies suggest that while normalisation of values to UCr may be valid for the evaluation of CKD and prediction of AKI sequelae and occurrences, it could be inappropriate for the diagnosis of AKI, or in the presence of certain acute kidney disease states.

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Elevation of serum and urine levels of TIMP-1 and tenascin in patients with renal disease

Abstract: Urinary concentrations of tenascin and TIMP-1 are elevated in association with renal disease and may reflect specific aspects of renal fibrosis.

Cited by 78 publications

References 31 publications

Role of matrix metalloproteinases in renal pathophysiologies

Role of matrix metalloproteinases in renal pathophysiologies

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

Normalisation of urinary biomarkers to creatinine for clinical practice and research – when and why

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