The Matrix Metalloproteinase Family

Woessner, Jeff

doi:10.1016/b978-012545090-4/50002-1

Cited by 177 publications

(195 citation statements)

References 23 publications

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“…Whether inactivation predominates over proenzyme activation would depend on ROS generation and concentration, which would correlate closely with the extent of inflammation. This mechanism provides an alternative pathway of MMP inactivation typically ascribed to protein inhibitors, such as TIMPs (Woessner, 1991;Woessner, 1998).…”

Section: Oxidative Control Of Mmp Activitymentioning

confidence: 99%

Control of matrix metalloproteinase catalytic activity

2007

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SummaryAs their name implies, MMPs were first described as proteases that degrade extracellular matrix proteins, such as collagens, elastin, proteoglycans, and laminins. However, studies of MMP function in vivo have revealed that these proteinases act on a variety of extracellular protein substrates, often to activate latent forms of effector proteins, such as antimicrobial peptides and cytokines, or to alter protein function, such as shedding of cell-surface proteins. Because their substrates are diverse, MMPs are involved in variety of homeostatic functions, such as bone remodeling, wound healing, and several aspects of immunity. However, MMPs are also involved in a number of pathological processes, such as tumor progression, fibrosis, chronic inflammation, tissue destruction, and more. A key step in regulating MMP proteolysis is the conversion of the zymogen into an active proteinase. Several proMMPs are activated in the secretion pathway by furin proprotein convertases, but for most the activation mechanisms are largely not known. In this review, we discuss both authentic and potential mechanisms of proMMP activation.

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Section: Oxidative Control Of Mmp Activitymentioning

confidence: 99%

Control of matrix metalloproteinase catalytic activity

2007

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“…Fifth, the orderly degradation of ECCM, critical for growth, remodeling and repair, 36,40 is mediated mainly by MMPs (Table 5). 30,31 The collagenases (MMP-1, -8, and -13) are highly specific and primarily cleave fibrillar collagens at specific sites, thereby destroying structural integrity with the minimum amount of proteolysis. The gelatinases (MMP-2 and -9) degrade the denatured fibrillar collagens, other collagen types, and elastins.…”

Section: Ventricular Remodeling After MI and The Role Of Eccmmentioning

confidence: 99%

“…• ACE inhibitors 7,11,28 • Parathormone 7,42 • ARBs 7,11 • Thyroid hormone 7,42 • Bradykininase inhibitors 7 • Glucocorticoids 7,41,42 • Endothelin antagonists 7,29 • Steroid hormones 7,41,42 • Chymase inhibitors 7 • Vasopeptidase inhibitors • TIMP inhibitors 30,31 • Bradykinin…”

Section: Eccm Degradation Proinflammatory Cytokines Healing and Rementioning

confidence: 99%

Ventricular Remodeling After Infarction and the Extracellular Collagen Matrix

2003

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L eft ventricular (LV) remodeling after myocardial infarction (MI) contributes significantly to LV dilation and dysfunction, and disability and death. Two paradigms, pertinent to antiremodeling therapy after MI (Figure 1), have evolved over the last 3 decades. Paradigm 1, LV remodeling is a major mechanism for disability and death, 1,2 has received a great deal of attention. In contrast, paradigm 2, remodeling of the extracellular collagen matrix (ECCM) plays a major role in LV remodeling, [3][4][5][6][7] whereby decrease, disruption, and/or defective composition of the ECCM promote LV dilation and rupture, 4 -7 has received little attention. A host of clinical trials showed that angiotensin-converting enzyme (ACE) inhibitors (ACE-Is) with or without aldosterone antagonists, angiotensin II (AngII) type 1 (AT 1 ) receptor blockers (ARBs), ␤-adrenergic blockers or reperfusion improve outcome in survivors of MI. 8 -10 Concurrent evidence has underscored the importance of preserving the ECCM during healing after MI. [2][3][4][5][6][7] However, the antifibrotic action of ACE-Is, aldosterone antagonists and ARBs on ECCM in the infarct zone (IZ) and noninfarct zone (NIZ), 6,7,9,11 and the reperfusion-induced damage to the ECCM in the IZ, 5,7,12 remain unreconciled with the benefits. 8 -10,13 Nevertheless, excessive ECCM, as in dilated ischemic cardiomyopathy after remote MI, 14,15 can contribute to LV diastolic dysfunction and poor outcome, 6 suggesting that antifibrotic drugs that target excess ECCM might be a logical therapeutic approach. This review focuses on the role of the ECCM in the evolution of LV remodeling after MI and the potential impact of therapies that target the ECCM. Ventricular Remodeling After MI and the Role of ECCMFive points merit emphasis. First, the LV remodeling process after MI is complex, dynamic, and time dependent, and progresses in parallel with healing over months. 1,2,7,16 Notably, it involves differential changes between the IZ and NIZ with respect to the following: (1) LV structure, shape, and topography 1,2 ( Figure 1); (2) cell type, such as myocytes and nonmyocytes (Table 1) 6,7,[17][18][19][20][21][22][23] ; (3) proteins, cytokines, and growth factors 7,24,25 ; and (4) the ECCM. 5-7,13-17,19 -23 Differential regional remodeling of the ECCM contributes significantly to global LV structural remodeling after MI (Figure 2) 7,9,26 and plays a pivotal role in paradigm 1. 3,6,7 Second, the post-MI heart shows remarkable capacity to adapt to the rather sudden development of an IZ and a NIZ. Thus, MI results in time-dependent damage to myocytes, nonmyocytes, and the ECCM in the IZ; ventricular dysfunction followed by volume overload and progressive dilation; reactive hypertrophy with interstitial fibrosis and increased collagen in the NIZ; gradual reparative fibrosis in the IZ 27 ; and vascular remodeling in the IZ and NIZ. 7 Third, several endogenous molecules that affect collagen synthesis and are upregulated after MI, and several agents that are used therapeutically for MI, affect co...

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“…Matrix metalloproteinases (MMPs) are the major effectors of tissue remodelling in vertebrates (Woessner, 1998). Molecular substrates for the MMPs include all classes of extracellular matrix (ECM) proteins, as well as a variety of other molecules involved in determining tissue structure and controlling tissue remodelling (Woessner, 1998;Vu and Werb, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…Molecular substrates for the MMPs include all classes of extracellular matrix (ECM) proteins, as well as a variety of other molecules involved in determining tissue structure and controlling tissue remodelling (Woessner, 1998;Vu and Werb, 2000). The MMP gelatinase A (gelA; MMP-2) is present in bodily fluids, including the aqueous humour (Ando et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinase gelatinase B (MMP-9) is associated with leaking glaucoma filtering blebs

Chintala¹,

Wang²,

Diskin³

et al. 2005

Experimental Eye Research

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The goal of glaucoma filtering surgery is to create a low resistance pathway for aqueous outflow. The result is a blister or 'bleb' on the conjunctiva, from which fluid drains into the vasculature. Filtering surgery results may be compromised if blebs develop leaks, a problem that surfaces more frequently when antimetabolites are used to control the wound healing response. We investigated the role of tissue remodelling enzymes of the Matrix metalloproteinase (MMP) family in the development of bleb leaks. Our design was a case series. We enrolled glaucoma patients with leaking blebs, glaucoma patients with overhanging blebs and normal eyes. Leaking bleb tissues (n = 11) and bleb leak fluid were collected from patients undergoing bleb revision surgery. Overhanging bleb tissues (from non-leaking blebs, n = 3), normal conjunctiva (n = 8), and aqueous humour (n = 4) were collected for comparison. Samples were analysed for MMP content and proteinase activity by the methods of zymography, westernblotting, immunohistochemistry, and in situ zymography. Our main outcome measures were presence and activity of MMP in sample.Zymography revealed the presence of a high molecular weight caseinase and a 92-kDa gelatinase of a size appropriate for the proenzyme form of gelatinase B (gelB; MMP-9), in extracts from leaking bleb tissue, but not in bleb leak fluid or aqueous humour samples. In contrast, a 65-kDa gelatinase of a size appropriate for gelatinase A (MMP-2) proenzyme was observed in all samples. All proteinases disappeared when 10 mM EDTA was added to the development buffer, consistent with their identity as MMPs. Western blotting and immunohistochemical analyses confirmed the identity of the 92 kDa proteinase as gelB, and further revealed its absence from extracts of overhanging bleb tissue and normal conjunctiva. In situ zymography demonstrated strong gelatinolytic activity in leaking bleb tissue, but not overhanging bleb tissue or normal conjunctiva.

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The Matrix Metalloproteinase Family

Cited by 177 publications

References 23 publications

Control of matrix metalloproteinase catalytic activity

Control of matrix metalloproteinase catalytic activity

Ventricular Remodeling After Infarction and the Extracellular Collagen Matrix

Matrix metalloproteinase gelatinase B (MMP-9) is associated with leaking glaucoma filtering blebs

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