Assessment of Serum Matrix Metalloproteinases MMP-2 and MMP-9 After Human Liver Transplantation: Increased Serum MMP-9 Level in Acute Rejection

Kuyvenhoven, J.; Verspaget, Hein W.; Gao, Qiang; Ringers, J.; Smit, Vincent T.H.B.M.; Lamers, C. B. H. W.; Hoek, Bart van

doi:10.1097/01.tp.0000131170.67671.75

Cited by 43 publications

(33 citation statements)

References 27 publications

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“…(1), but occurred independent of the genotype. Serum levels of MMP-9 peak at 1 week after OLT, which is associated with acute allograft Statistical significance X = 9.9; P = 0.002 rejection, as previously reported [14]. Irrespective of a genotype mismatch between the donor and the recipient, we found a comparable serum MMP-9 peak and pattern over time (Fig.…”

Section: The Role Of Mmp Polymorphisms In Liver Transplantationsupporting

confidence: 85%

“…The extracellular matrix may also be an important target in the process of acute rejection after orthotopic liver transplantation (OLT). In a previous study we demonstrated elevated serum levels of MMP-9 at 1 week after OLT in patients with acute allograft rejection [14].…”

Section: Introductionmentioning

confidence: 76%

“…Differences in MMP levels according to the genotype and disease complications were assessed by the MannWhitney U or the Wilcoxon signed ranks test for nonparametric data [14,23]. MMP levels are expressed as mean ± S.E.M.…”

Section: Discussionmentioning

confidence: 99%

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MMP-2 and MMP-9 Serum Levels Change but their Gene Promoter Polymorphisms are not Associated with Late Phase I/R Injury or Rejection after Orthotopic Liver Transplantation

Hove¹,

Rooij²,

Hoek³

et al. 2008

TOTRANSJ

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Abstract:Introduction. Matrix metalloproteinases (MMPs) are involved in connective tissue remodeling processes associated with chronic liver disease and complications after orthotopic liver transplantation (OLT). Genetic variations in the promoter region of the MMP-2 and MMP-9 genes are thought to contribute not only to their transcription rate but may also have predisposing clinical impact. Methods. MMP-2 and MMP-9 gene promoter polymorphisms were analyzed in 109 patients who underwent an OLT. The relationship between these MMP polymorphisms in the donor and recipient DNA with the development of ischemia/reperfusion (I/R) injury and rejection after OLT was evaluated. In addition, serum MMP-2 and MMP-9 levels were determined to illustrate potential phenotypical consequences in these patients. Results. The MMP-2 and -9 genotypes of the donor and recipient or a donor/recipient mismatch and chimerism were not associated with the development of late phase I/R injury or rejection in the OLT patients, although serological differences in the MMP levels did occur. The MMP-2 and -9 genotype distribution did also not have a major impact on the respective serum levels in patients that underwent an OLT. Conclusions. MMP-2 and MMP-9 gene polymorphisms do not seem to contribute to late phase I/R injury or rejection after liver transplantation. Serological changes in the MMP-2 and MMP-9 levels appear to occur independent of the MMP genotype after transplantation of the liver.

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Section: The Role Of Mmp Polymorphisms In Liver Transplantationsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 76%

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MMP-2 and MMP-9 Serum Levels Change but their Gene Promoter Polymorphisms are not Associated with Late Phase I/R Injury or Rejection after Orthotopic Liver Transplantation

Hove¹,

Rooij²,

Hoek³

et al. 2008

TOTRANSJ

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“…We also looked for any expression differences in extracellular matrix proteins in AR, because some of these have been previously demonstrated to be differentially expressed in AR. 15 We observed that whereas UMOD gene expression in AR biopsy was significantly lower in AR [false discovery rate (FDR) ϭ 0.02%; similar results to the low UMOD peptide abundance in AR urine], the three collagen genes (COL1A2, FDR ϭ 0.18%; COL3A1, FDR ϭ 0.67%; COL4A1, FDR ϭ 1.82%) were upregulated in AR (different from low collagen peptide abundance in AR urine). Gene expression for matrix metalloproteinase-7 (MMP-7; FDR ϭ 0.03%), tissue inhibitor of metalloproteinase 1 (TIMP1; FDR ϭ 24%), and the serpin peptidase inhibitor (SERPING1; FDR ϭ 33%) was higher in AR when compared with STA biopsies, although only MMP7 expression was significant.…”

Section: Integrated Analysis Of Matched Samples: Transcriptional Analmentioning

confidence: 51%

Integrative Urinary Peptidomics in Renal Transplantation Identifies Biomarkers for Acute Rejection

Ling

Sigdel²,

Lau³

et al. 2010

Journal of the American Society of Nephrology

123

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Noninvasive methods to diagnose rejection of renal allografts are unavailable. Mass spectrometry followed by multiple-reaction monitoring provides a unique approach to identify disease-specific urine peptide biomarkers. Here, we performed urine peptidomic analysis of 70 unique samples from 50 renal transplant patients and 20 controls (n ϭ 20), identifying a specific panel of 40 peptides for acute rejection (AR). Peptide sequencing revealed suggestive mechanisms of graft injury with roles for proteolytic degradation of uromodulin (UMOD) and several collagens, including COL1A2 and COL3A1. The 40-peptide panel discriminated AR in training (n ϭ 46) and test (n ϭ 24) sets (area under ROC curve Ͼ0.96). Integrative analysis of transcriptional signals from paired renal transplant biopsies, matched with the urine samples, revealed coordinated transcriptional changes for the corresponding genes in addition to dysregulation of extracellular matrix proteins in AR (MMP-7, SERPING1, and TIMP1). Quantitative PCR on an independent set of 34 transplant biopsies with and without AR validated coordinated changes in expression for the corresponding genes in rejection tissue. A six-gene biomarker panel (COL1A2, COL3A1, UMOD, MMP-7, SERPING1, TIMP1) classified AR with high specificity and sensitivity (area under ROC curve ϭ 0.98). These data suggest that changes in collagen remodeling characterize AR and that detection of the corresponding proteolytic degradation products in urine provides a noninvasive diagnostic approach.

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“…In addition, MMP-9 (gelatinase B), a member of MMPs, is derived mainly from Kupffer cells in the liver, 38 and its expression is significantly increased together with the activation of cells, indicating that MMP-9 could be a marker of Kupffer cell activation instead of its activity as a collagenase. A number of studies have shown increased serum and plasma levels of MMP-9 in various types Pathophysiology of steatohepatitis Y-p Mu et al of liver injury, including ischemic reperfusion injury 39 and chronic viral hepatitis. 40,41 Furthermore, the mutation of MMP-9 was reported to inhibit hepatic fibrogenesis in mice.…”

Section: Discussionmentioning

confidence: 99%

Reversibility of fibrosis, inflammation, and endoplasmic reticulum stress in the liver of rats fed a methionine–choline-deficient diet

Ogawa

Kawada

2010

Laboratory Investigation

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Fatty liver disease has become a health problem related to metabolic syndrome worldwide, although its molecular pathogenesis requires further study. It is also unclear whether advanced fibrosis of steatohepatitis will regress when diet is controlled. The aim of this study was to investigate whether the resolution of fibrosis occurs in steatohepatitis induced by a methionine-choline-deficient diet (MCDD). Manifestation of endoplasmic reticulum (ER) stress in this model was also studied. Nonalcoholic steatohepatitis with advanced fibrosis was induced in rats by feeding them an MCDD for 10 weeks. Instead of MCDD, a methionine-choline control diet (CD) was given for the last 2 weeks to the experimental group. Fibrosis and inflammation were determined by tissue staining. Protein and gene expressions were determined by immunoblotting and quantitative reverse transcription-PCR (RT-PCR), respectively. Expressions of caspase-7, caspase-12, glucose-regulated protein 78 (GRP78), and protein disulfide isomerase were evaluated to clarify the presence of ER stress. Changing the diet from MCDD to CD triggered the reduction of fat in hepatocytes, a decrease in inflammatory gene expression and oxidative stress, and regression of fibrosis accompanied by the disappearance of activated stellate cells and macrophages. Immunohistochemistry, immunoblotting, and RT-PCR analysis all indicated the occurrence of ER stress in steatohepatitis, while it recovered immediately after changing the diet from MCCD to CD. The ratio of hepatocyte proliferation/apoptotis increased significantly during the recovery stage. This simple experiment clearly shows that changing the diet from MCDD to a normal diet (CD) triggers the resolution of hepatic inflammatory and fibrotic reactions and hepatocyte apoptosis, suggesting that MCDD-induced steatohepatitis is also reversible. ER stress appears and disappears in association with the generation and regression of steatohepatitis, respectively, with fibrosis.

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Assessment of Serum Matrix Metalloproteinases MMP-2 and MMP-9 After Human Liver Transplantation: Increased Serum MMP-9 Level in Acute Rejection

Cited by 43 publications

References 27 publications

MMP-2 and MMP-9 Serum Levels Change but their Gene Promoter Polymorphisms are not Associated with Late Phase I/R Injury or Rejection after Orthotopic Liver Transplantation

MMP-2 and MMP-9 Serum Levels Change but their Gene Promoter Polymorphisms are not Associated with Late Phase I/R Injury or Rejection after Orthotopic Liver Transplantation

Integrative Urinary Peptidomics in Renal Transplantation Identifies Biomarkers for Acute Rejection

Reversibility of fibrosis, inflammation, and endoplasmic reticulum stress in the liver of rats fed a methionine–choline-deficient diet

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