Structure and function of matrix metalloproteinases and TIMPs

Nagase, Hideaki; Visse, Robert; Murphy, Gillian

doi:10.1016/j.cardiores.2005.12.002

Cited by 2,820 publications

(2,731 citation statements)

References 115 publications

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“…Some reports in the literature show that MMP-9 plays an important role in the degradation of the BM as a result of its ability to degrade collagen IV. 16 Nagase et al 30 and Verma and Hansch 31 demonstrated that MMPs are weakly expressed by tissues under physiologic conditions, whereas high expression of these proteins is observed in neoplastic tissues, owing to an imbalance in the activity of MMPs and their inhibitors (TIMPs). In the present study, high percentage and diffuse expression of TIMP-2 was observed in epithelial and mesenchymal cells of DCs, RCs, and KOTs.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of the immunohistochemical expression of collagen IV, MMP-9, and TIMP-2 in odontogenic cysts and tumors

Henriques

Vasconcelos

Galvão

et al. 2011

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, an

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Objective. The aim of this study was to evaluate the immunohistochemical expression of collagen IV, matrix metalloproteinase (MMP) 9 and tissue inhibitor of MMP (TIMP) 2 in dentigerous cysts (DCs), radicular cysts (RCs), keratocystic odontogenic tumors (KOTs), and ameloblastomas. Study design. Twenty cases of DCs, 20 RCs, 20 KOTs, and 20 ameloblastomas were selected and analyzed by immunohistochemistry. Results. Most DCs and RCs showed continuous and Ͼ50% staining for collagen IV in the basement membrane of the epithelium, whereas predominantly discontinuous thin and Յ50% staining was observed in KOTs and ameloblastomas, with a significant difference in staining percentage (P Ͻ .001). MMP-9 was diffusely distributed and localized in both epithelial and mesenchymal cells of all of the lesions analyzed. The staining percentage was higher in the epithelium (P ϭ .058) and mesenchyme (P ϭ .005) of KOTs and ameloblastomas. Moreover, the distribution pattern, location, and percentage of expression of TIMP-2 were similar in the lesions studied, except for ameloblastoma, with a significant difference in staining percentage (P Ͻ .001).Conclusion. These results demonstrate that the interaction between collagen IV, MMP-9, and TIMP-2 is an important factor for the establishment of differences in the biologic behavior of the odontogenic cysts and tumors studied. Factors related to the epithelial and mesenchymal components participate in the regulation of the growth of odontogenic cystic lesions and tumors. 1 The altered expression of specific proteins of the extracellular matrix (ECM), associated with the exuberant presence of matrix metalloproteinases (MMPs) and the absence of expression of metalloproteinase inhibitors (TIMPs), may influence the behavior of these lesions. In the case of tumors, this situation contributes to the growth and higher aggressiveness of the tumor. 2 The odontogenic keratocyst, recently reclassified as keratocystic odontogenic tumor (KOT), 3 is known for its aggressive nature and high rate of recurrence, especially compared with other odontogenic cysts. 4 Ameloblastoma is a locally aggressive benign epithelial odontogenic tumor with a marked invasion potential that results in multiple recurrences after enucleation and curettage. 5 In contrast, dentigerous (DC) and radicular (RC) cysts show an indolent behavior and rarely recur after surgical removal. KOT presents a cystic structure similar to that of DC and RC, but its invasive and destructive growth is similar to that of ameloblastoma. 6 KOT, ameloblastoma, DC, and RC show distinct evolutions and biologic behaviors. In view of this fact, a growing number of studies have tried to identify

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Section: Discussionmentioning

confidence: 99%

Comparative analysis of the immunohistochemical expression of collagen IV, MMP-9, and TIMP-2 in odontogenic cysts and tumors

Henriques

Vasconcelos

Galvão

et al. 2011

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, an

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“…MMPs require posttranslational activation, and active enzymes are then controlled by TIMPs (44). In cartilage, procollagenase activation mechanisms represent a key control point and may not be observed even with prolonged inflammatory cytokine stimulation in vitro (45).…”

Section: Discussionmentioning

confidence: 99%

Modulation of aggrecan and ADAMTS expression in ovine tendinopathy induced by altered strain

Smith

Sakurai

Smith

et al. 2008

Arthritis & Rheumatism

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Objective. To evaluate histologic, immunohistochemical, and molecular changes in tendon induced by altered strain in a large-animal model.Methods. A full-thickness partial-width laceration of the infraspinatus tendon was created in 5 sheep, while 5 sham-operated sheep were used as controls. Sheep were killed after 4 weeks, and 4 differentially stressed tendon regions (tensile or near bone attachment from overstressed or stress-deprived halves) were evaluated for histopathology, proteoglycan (PG) accumulation, and characterization of glycosaminoglycans and aggrecan catabolites. Gene expression of matrix components, enzymes, and inhibitors was analyzed by reverse transcriptase-polymerase chain reaction.Results. Histopathologic changes were detected in both overstressed and stress-deprived tensile tendon, but only in stress-deprived tendon near bone. In overstressed and stress-deprived tensile tendon, levels of keratan sulfate, chondroitin 4-sulfate, and chondroitin 6-sulfate were increased. In overstressed tensile tendon, levels of ADAMTS-generated aggrecan catabolites were increased. There was increased matrix metalloproteinase 13 (MMP-13) and decreased fibromodulin and decorin expression in all regions. Increased MMP-1, MMP-9, MMP-14, and ADAMTS-1 expression, and decreased type II collagen expression were restricted to stress-deprived tendon. In stress-deprived boneattachment regions, messenger RNA (mRNA) for aggrecan was decreased, and ADAMTS was increased. In overstressed tensile tendon, aggrecan mRNA was increased, and ADAMTS was decreased.Conclusion. The distinct molecular changes in adjacent tissue implicate altered strain rather than humoral factors in controlling abnormal tenocyte metabolism, and highlight the importance of regional sampling. Tendon abnormalities induced by increased strain are accompanied by increased aggrecan, decreased ADAMTS, and low PG expression, which may negatively impact the structural integrity of the tissue and predispose to rupture.Injuries of the shoulder due to overuse are increasingly prevalent in both the sporting arena and the workplace. Occupational injury of the shoulder is second only to neck and low back pain in the frequency of consultation by general practitioners, with the most common injury involving the rotator cuff. (1,2) The prevalence of rotator cuff conditions increases with age, from 30-50% in the seventh decade of life to a staggering 70-80% by the ninth (3,4). Although most cases are treated conservatively, many patients undergo surgical repair with a prolonged convalescence. There are no drugs to specifically treat disorders of the rotator cuff or other tendons, and many surgical repairs fail within 12 months (5). Lack of knowledge of the fundamental mechanisms that underlie tendon breakdown results in limited and inadequate management options for tendon disorders.

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“…To determine whether the differential sensitivity to collagen-induced apoptosis could be related to the cell capacity to remodel the matrix, we analyzed by reverse transcriptase-PCR the expression profile of five secreted (MMP-1, -2, -8, -9 and -13) and three membrane-type MMPs (MMP-14 or MT1-MMP, known to cleave COL1 (Morrison and Overall, 2006;Nagase et al, 2006;Sabeh et al, 2009a). Most MMPs were expressed at variable levels in the different cell lines (Figure 2a).…”

Section: Mmp-14 Protects Cells Against Col1-induced Apoptosismentioning

confidence: 99%

“…To date, type I collagenolytic activity is confined to a small subset of proteinases belonging to either the cysteine proteinase or matrix metalloproteinase (MMP) families (BirkedalHansen, 1987;Nagase et al, 2006;Sabeh et al, 2009a). MMPs are zinc-dependent endopeptidases that play crucial roles in cancer progression (Noe¨l et al, 2008;Kessenbrock et al, 2010), not only by degrading physical ECM barriers, but also by regulating the processing of an increasing panel of molecular mediators of signaling events (Lopez-Otin and Hunter, 2010;Rodrı´guez et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

MT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis

et al. 2011

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As invading breast carcinoma cells breach their underlying basement membrane, they become confronted with a dense three-dimensional reactive stroma dominated by type I collagen. To develop metastatic capabilities, invading tumor cells must acquire the capacity to negotiate this novel microenvironment. Collagen influences the fate of epithelial cells by inducing apoptosis. However, the mechanisms used by invading tumor cells to evade collagen-induced apoptosis remain to be defined. We demonstrate that membrane type-1 matrix metalloproteinase (MT1-MMP/MMP-14) confers breast cancer cells with the ability to escape apoptosis when embedded in a collagen gel and after orthotopic implantation in vivo. In the absence of MMP-14-dependent proteolysis, type I collagen triggers apoptosis by inducing the expression of the pro-apoptotic Bcl-2-interacting killer in luminallike breast cancer cells. These findings reveal a new mechanism whereby MMP-14 activity promotes tumor progression by circumventing apoptosis.

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Structure and function of matrix metalloproteinases and TIMPs

Cited by 2,820 publications

References 115 publications

Comparative analysis of the immunohistochemical expression of collagen IV, MMP-9, and TIMP-2 in odontogenic cysts and tumors

Comparative analysis of the immunohistochemical expression of collagen IV, MMP-9, and TIMP-2 in odontogenic cysts and tumors

Modulation of aggrecan and ADAMTS expression in ovine tendinopathy induced by altered strain

MT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis

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