Degradation of entactin by matrix metalloproteinases. Susceptibility to matrilysin and identification of cleavage sites.

Sires, Ulrike I.; Griffin, Gail L.; Broekelmann, Thomas J.; Mecham, Robert P.; Murphy, Gillian; Chung, Albert E.; Welgus, Howard G.; Senior, Robert M.

doi:10.1016/s0021-9258(18)53963-6

Cited by 115 publications

(16 citation statements)

References 37 publications

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“…MMP-7 and MMP-3 were originally thought to be similar enzymes because of their specificity for various extracellular macromolecules [9]. However, recent studies on the substrates of MMP-7 have demonstrated that it has a higher specificity constant for many extracellular matrix components, such as proteoglycans, tenascin, vitronectin, entactin and cartilage link protein, and generates dissimilar degradation products [9,[25][26][27][28]. The digestion of DCN is similar since MMP-7 degrades it preferentially into different fragments from those obtained with MMP-3.…”

Section: Discussionmentioning

confidence: 99%

Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-β1 release

Imai

Hiramatsu

Fukushima

et al. 1997

Biochemical Journal

411

255

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Decorin (DCN) is a ubiquitous proteoglycan comprised of a core protein attached to a single dermatan/chondroitin sulphate glycosaminoglycan chain. It may play a role in regulation of collagen fibrillogenesis and function as a reservoir of transforming growth factor beta (TGF-beta) in the extracellular milieu. We have examined the susceptibility of DCN to five different matrix metalloproteinases (MMPs): MMP-1 (tissue collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1), MMP-7 (matrilysin) and MMP-9 (gelatinase B). MMP-2 and MMP-3 digest DCN into seven major fragments in a similar pattern. The N-terminal sequence of the two fragments generated by MMP-2 and MMP-3 is Leu211-Lys-Gly-Leu-Asn, but that of the others is Asp1-Glu-Ala-Ser-Gly. MMP-7 cleaves DCN into three major fragments which have the N-termini Asp1-Glu-Ala-Ser-Gly, Glu2-Ala-Ser-Gly-Ile and Leu244-His-Leu-Asp-Asn. Activities of MMP-1 and MMP-9 against DCN are negligible. The values of Km for the MMPs capable of degrading DCN are very similar (10-12 microM), but the kcat/Km value for MMP-7 (30.5 microM-1.h-1) is 4.5-fold higher than those for MMP-2 and MMP-3. Incubation of a DCN-TGF-beta1 complex with MMP-2, -3 or -7 results in release of TGF-beta1 from the complex. These data indicate proteolytic degradation of DCN by MMP-2, MMP-3 and MMP-7, and suggest the possibility that, under pathophysiological conditions, the digestion by the MMPs may induce tissue reactions mediated by TGF-beta1 released from DCN in the connective tissues.

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Section: Discussionmentioning

confidence: 99%

Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-β1 release

Imai

Hiramatsu

Fukushima

et al. 1997

Biochemical Journal

411

255

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“…The meprin A cleavage site is at position 899 to 900, a glutamine-glycine (gln-gly) site in the nidogen molecule. Comparison of the 55 kDa fragment cleavage site with over 50 nidogen cleavage sites produced by granule stored proteases, blood proteases, matrix metalloproteinases and trypsin revealed that the meprin A-induced nidogen cleavage site (gln-gly) is unique (Table 1) [13,14]. This unique nidogen fragment contains the laminin binding site in the G-3 region (Fig.…”

Section: Examination Of the Cleavage Sitementioning

confidence: 99%

Meprin A, the major matrix degrading enzyme in renal tubules, produces a novel nidogen fragmentin vitro andin vivo

Walker¹,

Kaushal²,

Shah³

1998

Kidney International

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We examined the effect of meprin A, the major matrix degrading metalloproteinase in rat kidney, on the laminin-nidogen complex. N-terminal sequence information from the most abundant 55 kDa fragment revealed that it was a breakdown product of nidogen rather than laminin. In comparison with over 50 nidogen cleavage sites produced by other proteases, the meprin A-induced nidogen cleavage site at amino acid position 899-900, a glutamine-glycine site in the G3 domain, is unique. In addition, these data demonstrate that meprin A degrades the G3 domain of nidogen even in the presence of laminin binding, which usually accords protection from proteolytic degradation. Meprin A also degraded purified nidogen into similar breakdown products. Given that the tubular basement membrane is located on the basilar side of the cell, the location of meprin A on the apical brush border makes it difficult to envision a role for meprin A in injury-induced basement membrane component breakdown. Thus, we examined the possibility that following renal tubular epithelial cell injury, meprin A undergoes a translocation to reach the underlying basement membrane. After renal ischemia-reperfusion there was a marked alteration in meprin A staining with meprin A now distributed throughout the renal tubular cell cytoplasm and directly adherent to the tubular basement membrane. This was in contrast to the usual linear staining of the brush border of tubules in the corticomedullary junction. These data provide unequivocal evidence that following injury, meprin A undergoes redistribution and/or adherence to the tubular basement membrane. Since in our in vitro studies, we identified a distinct meprin-induced 55 kDa nidogen breakdown product, the urine was also examined for the presence of nidogen degradation products after rat renal ischemia-reperfusion injury. Western blots showed a marked increase in the urinary 55 kDa nidogen fragment as early as the first day following ischemia-reperfusion injury and continuing for six days. Taken together, these in vivo data strongly support the notion that the nidogen breakdown products are the result of partial degradation of tubular basement membrane by meprin A following renal tubular ischemia-reperfusion injury.

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“…6 Substrates for MMP-9 include collagen types I and IV, fibrinogen, and a molecule that assists in the bridging of type IV collagen. 11,12 Many of the initial studies involving MMP-9 analysis were centered on ex vivo analysis of the aortic wall. Changes are present in genes that regulate MMP production in patients with known AAAs.…”

Section: Matrix Metalloproteinase-9mentioning

confidence: 99%

An Overview of Matrix Metalloproteinases in the Pathogenesis and Treatment of Abdominal Aortic Aneurysms

Keeling¹,

Armstrong²,

Stone³

et al. 2005

Vasc Endovascular Surg

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Recent basic and clinical research has established a link between the pathogenesis of abdominal aortic aneurysms (AAA) and matrix metalloproteinases (MMP). The discovery of the influence of MMPs on in vitro and in vivo aneurysm development has yielded promising information that may eventually decode the pathogenetic factors affecting the initiation and growth rate of AAAs. In this review, an analysis of MMPs involved in AAA disease is presented, including the data from recent research studies and planned clinical drug trails designed to retard the AAA growth by inhibiting MMP activity.

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Degradation of entactin by matrix metalloproteinases. Susceptibility to matrilysin and identification of cleavage sites.

Cited by 115 publications

References 37 publications

Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-β1 release

Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-β1 release

Meprin A, the major matrix degrading enzyme in renal tubules, produces a novel nidogen fragmentin vitro andin vivo

An Overview of Matrix Metalloproteinases in the Pathogenesis and Treatment of Abdominal Aortic Aneurysms

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