Cloning of the Human Tissue Inhibitor of Metalloproteinase-4 Gene (TIMP4) and Localization of the TIMP4 andTimp4Genes to Human Chromosome 3p25 and Mouse Chromosome 6, Respectively

Olson, Timothy M.; Hirohata, Satoshi; Ye, Jean; Leco, Kevin J.; Seldin, Michael F.

doi:10.1006/geno.1998.5362

Cited by 33 publications

(19 citation statements)

References 18 publications

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“…TIMP-4 was first identified in 1996 through sequencing a human heart cDNA library and maps to the human 3p25 chromosome (243,311). This study and others demonstrated a very robust signal for TIMP-4 mRNA within the myocardium, but not in other organ systems (27,136,243).…”

Section: E the Timpsmentioning

confidence: 60%

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Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

Spinale¹

2007

Physiological Reviews

1,004

1,023

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It is now becoming apparent that dynamic changes occur within the interstitium that directly contribute to adverse myocardial remodeling following myocardial infarction (MI), with hypertensive heart disease and with intrinsic myocardial disease such as cardiomyopathy. Furthermore, a family of matrix proteases, the matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs), has been recognized to play an important role in matrix remodeling in these cardiac disease states. The purpose of this review is fivefold: 1) to examine and redefine the myocardial matrix as a critical and dynamic entity with respect to the remodeling process encountered with MI, hypertension, or cardiomyopathic disease; 2) present the remarkable progress that has been made with respect to MMP/TIMP biology and how it relates to myocardial matrix remodeling; 3) to evaluate critical translational/clinical studies that have provided a cause-effect relationship between alterations in MMP/TIMP regulation and myocardial matrix remodeling; 4) to provide a critical review and analysis of current diagnostic, prognostic, and pharmacological approaches that utilized our basic understanding of MMP/TIMPs in the context of cardiac disease; and 5) most importantly, to dispel the historical belief that the myocardial matrix is a passive structure and supplant this belief that the regulation of matrix protease pathways such as the MMPs and TIMPs will likely yield a new avenue of diagnostic and therapeutic strategies for myocardial remodeling and the progression to heart failure.

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Section: E the Timpsmentioning

confidence: 60%

“…TIMP-4 is the most recently identified member of the TIMP family, in which a high degree of expression occurs within the cardiovascular system, most notably the myocardium (27,136,243,311,416). TIMP-4 was first identified in 1996 through sequencing a human heart cDNA library and maps to the human 3p25 chromosome (243,311).…”

Section: E the Timpsmentioning

confidence: 99%

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

Spinale¹

2007

Physiological Reviews

1,004

1,023

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“…However, the expression and release of active MMP molecules does not establish matrix-degrading activity, since interactions with ubiquitous endogenous inhibitors determine enzymatic function in tissues. In this regard, most attention has focused on the TIMP family (19)(20)(21)(22)(23)(24)(25). However, previous work from several groups also implicated members of the serpin superfamily, i.e., α 2 -macroglobulin and RECK, in the regula- tion of MMP activity (33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

“…Such endogenous inhibitors were considered restricted to the family of tissue inhibitors of MMPs (TIMPs) (19)(20)(21)(22)(23)(24)(25). Interestingly, expression of this prototypical class of inhibitors does not correlate inversely with enhanced MMP activity in situ, as would be expected with increased matrix turnover (26,27).…”

Section: Tissue Factor Pathway Inhibitor-2 Is a Novel Inhibitor Of Mamentioning

confidence: 99%

Tissue factor pathway inhibitor-2 is a novel inhibitor of matrix metalloproteinases with implications for atherosclerosis

Herman

Sukhova²,

Kisiel³

et al. 2001

J. Clin. Invest.

202

130

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Degradation of ECM, particularly interstitial collagen, promotes plaque instability, rendering atheroma prone to rupture. Previous studies implicated matrix metalloproteinases (MMPs) in these processes, suggesting that dysregulated MMP activity, probably due to imbalance with endogenous inhibitors, promotes complications of atherosclerosis. We report here that the serine proteinase inhibitor tissue factor pathway inhibitor-2 (TFPI-2) can function as an MMP inhibitor. TFPI-2 diminished the ability of the interstitial collagenases MMP-1 and MMP-13 to degrade triple-helical collagen, the primary load-bearing molecule of the ECM within human atheroma. In addition, TFPI-2 also reduced the activity of the gelatinases MMP-2 and MMP-9. In contrast to the "classical" tissue inhibitors of MMPs (TIMPs), TFPI-2 expression in situ correlated inversely with MMP levels in human atheroma. TFPI-2 colocalized primarily with smooth muscle cells in the normal media as well as the plaque's fibrous cap. Conversely, the macrophage-enriched shoulder region, the prototypical site of matrix degradation and plaque rupture, stained only weakly for TFPI-2 but intensely for gelatinases and interstitial collagenases. Evidently, human mononuclear phagocytes, an abundant source of MMPs within human atheroma, lost their ability to express this inhibitor during differentiation in vitro. These findings establish a new, anti-inflammatory function of TFPI-2 of potential pathophysiological significance for human diseases, including atherosclerosis.

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“…The TIMP-1, -2, -3 and -4 family genes are localized on chromosomes Xp11-p11.4, 17q25, 22q12.1-13.2 and 3p25, respectively. The physiological activity of the TIMPs was studied by observing that TIMP-1, -3 and -4 expression is inducible and often tissue-specific, while TIMP-2 expression is constitutive and extensively expressed throughout the body (4)(5)(6)(7)(8). Deregulation of the MMP-TIMP balance can result in the progression of many human diseases, including cancer (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Tissue inhibitor of metalloproteinase 2 (TIMP-2) expression in adenocarcinoma pleural effusions

Giarnieri

Alderisio²,

Mancini³

et al. 2008

Oncol Rep

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Abstract. Serous effusions are frequently a clinical manifestation of metastatic disease, with lung, breast and ovarian carcinoma and mesothelioma leading the list. The diagnosis of malignant effusion signifies disease progression and is associated with a worsening patient prognosis. The ability to grow in a dense exudative fluid suggests that the malignant cells are capable of acquiring nutrients, surviving and proliferating, despite the lack of a solid-phase scaffold. During proliferation, neoplastic cells release ligands and matrix metalloproteinases (MMPs) into their environment, which dissolve the extracellular matrix (ECM). Tissue inhibitors of metalloproteinase (TIMPs) are endogenous regulators of MMPs, the principal enzymes responsible for the degradation of ECM in metastasis, and reduce their proteolytic activity. TIMP-2 has demonstrated an association between high tumor tissue expression levels and poor prognosis. The purpose of this preliminary study is to investigate, by immunocytochemistry, TIMP-2 expression in non-neoplastic and metastatic adenocarcinoma pleural effusions. We selected 16 cases of reactive mesothelio, 7 of normal mesothelio, 14 of lung adenocarcinoma, 9 from the ovary, 4 from the gastrointestinal tract and 3 from the breast. In 23/30 cases (76%), we detected adenocarcinoma cells with strong TIMP-2 expression. Positive TIMP-2 expression was found in 2/7 cases (28%) of normal and 2/16 (12%) of reactive mesothelio. A statistical association was detected between TIMP-2 expression and metastatic adenocarcinoma cells compared to reactive and normal mesothelial cells (p<0.00003). The calculated sensitivities for TIMP-2 compared to CEA and Ber-EP4 were, respectively, 76.7, 80.0 and 93.3%, and the specificities 82.6, 95.7 and 87.0%. In conclusion, immunocytochemical detection of TIMP-2 could be considered an interesting marker in metastatic adenocarcinoma pleural effusions, and could possibly be used as a component of an antibody panel in diagnostic cytopathology.

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Cloning of the Human Tissue Inhibitor of Metalloproteinase-4 Gene (TIMP4) and Localization of the TIMP4 andTimp4Genes to Human Chromosome 3p25 and Mouse Chromosome 6, Respectively

Cited by 33 publications

References 18 publications

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

Tissue factor pathway inhibitor-2 is a novel inhibitor of matrix metalloproteinases with implications for atherosclerosis

Tissue inhibitor of metalloproteinase 2 (TIMP-2) expression in adenocarcinoma pleural effusions

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