Diminished corneal angiogenesis in gelatinase A‐deficient mice

Kato, Takuji; Kure, Tomoko; Chang, Jin Hong; Gabison, Éric; Itoh, Takeshi; Itohara, Shigeyoshi; Azar, Dimitri T.

doi:10.1016/s0014-5793(01)02897-6

Cited by 121 publications

(84 citation statements)

References 11 publications

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“…This lack of vascular growth is recapitulated in an experimentally induced corneal angiogenesis assay 43 , which induces new blood-vessel growth in control mice. Blood-vessel growth is not observed in Mmp14 mutants 43 , whereas it is reduced but not eliminated in Mmp2-mutant animals 55 . In a laser-induced injury model of retinal degeneration, neovascularization is reduced in single Mmp2 and Mmp9 mutants and is strongly reduced in the Mmp2 Mmp9 double mutant, indicating that these MMPs function redundantly 56 .…”

Section: Mmps In Blood-vessel Remodellingmentioning

confidence: 85%

Matrix metalloproteinases and the regulation of tissue remodelling

Page-McCaw

Ewald

Werb

2007

Nat Rev Mol Cell Biol

2,560

2,180

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Matrix metalloproteinases (MMPs) were discovered because of their role in amphibian metamorphosis, yet they have attracted more attention because of their roles in disease. Despite intensive scrutiny in vitro, in cell culture and in animal models, the normal physiological roles of these extracellular proteases have been elusive. Recent studies in mice and flies point to essential roles of MMPs as mediators of change and physical adaptation in tissues, whether developmentally regulated, environmentally induced or disease associated.The founding member of the matrix metalloproteinase (MMP) family, collagenase, was identified in 1962 by Gross and Lapiere, who found that tadpole tails during metamorphosis contained an enzyme that could degrade fibrillar collagen 1,2 . Subsequently, an interstitial collagenase, collagenase-1 or MMP1, was found in diseased skin and synovium 3 . In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775-Ile776 or Gly775-Lys776 in native type I, II or III collagen molecules 3,4 . Further research led to the discovery of a family of structurally related proteinases (23 in human, 24 in mice), now referred to as the MMP family.Interest in MMPs increased in the late 1960s and early 1970s following observations that MMPs are upregulated in diverse human diseases including rheumatoid arthritis and cancer. Importantly, high levels of MMPs often correlated with poor prognosis in human patients (reviewed in REF. 5 ). However, recent clinical data indicate that the relationship between § These authors contributed equally to this paper. Competing interests statementThe authors declare no competing financial interests. DATABASESThe following terms in this article are linked online to: Entrez Genome: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene DmMmp1 | DmMmp2 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMMPs and disease is not simple; for example, increased MMP activity can enhance tumour progression or can inhibit it (reviewed in REF. 6 ). This complex relationship between MMP expression and cancer has increased the basic and clinical interest in understanding MMP function in vivo, but it has also focused attention on MMPs and pathology, and relatively less attention has been focused on the normal roles of these enzymes. MMP proteolysisMMPs are members of the metzincin group of proteases, which are named after the zinc ion and the conserved Met residue at the active site 11,12 . Recent work has generated a unified peptidase nomenclature 13 Functions of MMP proteolysisHistorically, MMPs were thought to function mainly as enzymes that degrade structural components of the ECM. However, MMP proteolysis can create space for cells to migrate, can produce specific substrate-cleavage fragments with independent biological activity, can MMPs in bone modelling and remodellingBone is an important site of ongoing tissue remodelling during development...

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Section: Mmps In Blood-vessel Remodellingmentioning

confidence: 85%

Matrix metalloproteinases and the regulation of tissue remodelling

Page-McCaw

Ewald

Werb

2007

Nat Rev Mol Cell Biol

2,560

2,180

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“…The role for MMP-14 in activation of MMP-2 is further questioned by a lack of phenocopy between null mouse lines. Whereas MMP-2 null mice reveal mild phenotypes, mostly related to neovascularization and inflammation (Berglin et al, 2003;Corry et al, 2002;Itoh et al, 2002;Itoh et al, 1998;Kato et al, 2001;Ohno-Matsui et al, 2003), MMP-14 knock-out mice have severe defects in skeletal development and turnover of type I collagen (Holmbeck et al, 1999;Holmbeck et al, 2003;Zhou et al, 2000). Overall, the in vivo data indicate that MMP-14 is not required for activation of MMP-2, but they do not rule the possibility that other membrane-type MMPs might be involved.…”

Section: Activation Of Prommps By Mmpsmentioning

confidence: 97%

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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“…The bioactivity of purified laminin-5 ␥2 fragments was examined with an aortic ring assay as described previously (24). Briefly, a 96-well plate was covered with 50 l of Matrigel (BD Biosciences).…”

Section: Purification Of Cat S-generated Laminin-5 ␥2 Fragments and Amentioning

confidence: 99%

“…After 30 min of solidification, 100 l of Dulbecco's modified Eagle's medium without fetal calf serum, with or without purified laminin-5 ␥2 fragments, was added to each well to a final concentration of 10 ng/ml. The combination of bFGF (10 ng/ml) and interferon-␥ (500 units/ml) was used as a positive control (24). After 10 days of culture, the gels were photographed, and the endothelial outgrowth was analyzed by manually circulating and computing square pixels and quantified by Image-Pro Plus software.…”

Section: Purification Of Cat S-generated Laminin-5 ␥2 Fragments and Amentioning

confidence: 99%

Cathepsin S Controls Angiogenesis and Tumor Growth via Matrix-derived Angiogenic Factors

Wang

Sun

Kitamoto

et al. 2006

Journal of Biological Chemistry

251

196

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The cysteine protease cathepsin S is highly expressed in malignant tissues. By using a mouse model of multistage murine pancreatic islet cell carcinogenesis in which cysteine cathepsin activity has been functionally implicated, we demonstrated that selective cathepsin S deficiency impaired angiogenesis and tumor cell proliferation, thereby impairing angiogenic islet formation and the growth of solid tumors, whereas the absence of its endogenous inhibitor cystatin C resulted in opposite phenotypes. Although mitogenic vascular endothelial growth factor, transforming growth factor-␤1, and the anti-angiogenic endostatin levels in either serum or carcinoma tissue extracts did not change in cathepsin S-or cystatin C-null mice, tumor tissue basic fibroblast growth factor and serum type 1 insulin growth factor levels were higher in cystatin C-null mice, and serum type 1 insulin growth factor levels were also increased in cathepsin S-null mice. Furthermore, cathepsin S affected the production of type IV collagen-derived anti-angiogenic peptides and the generation of bioactive pro-angiogenic ␥2 fragments from laminin-5, revealing a functional role for cathepsin S in angiogenesis and neoplastic progression.Angiogenesis, the development of the microvasculature, is an essential process occurring under many pathological and physiological circumstances and depends on tightly controlled interactions between cells and extracellular matrix (ECM) 2 mediated by integral membrane proteins. These include integrins, which provide a link between ECM and the cytoskeleton, and extracellular proteases and their inhibitors, which mediate focal degradation of ECM components (1, 2), generate cell growth factors (3), and produce angiogenic regulatory factors (4).Lysosomal cysteine protease cathepsins have been shown to be highly expressed in human and murine tumors (5), where angiogenesis plays essential roles. Interruption of their expression either by antisense RNA (6) or RNA interference (7, 8) reduced tumor cell invasion, angiogenesis, and tumor growth. A recent study also demonstrated that inhibition of the activities of cysteine proteases with a broad inhibitor reduced angiogenesis and growth of pancreatic ␤-cell islet carcinoma in mice with an SV40 T antigen (Tag) transgene driven by the rat insulin II promoter (RIP1-Tag2) (9). Administration of JPM-ethyl ester (10), which affects all activities of cysteinyl cathepsins, significantly diminished the angiogenic switch, tumor burden, and tumor cell proliferation (11). However, many important questions are still unanswered; for example, which cathepsin(s) is the most important and by what mechanisms do these cysteinyl cathepsins affect tumor progression? Earlier studies suggested the importance of cathepsin (Cat) B in tumor angiogenesis and growth (6 -8). However, additional studies also demonstrated constitutive expression of Cat B in several cell types or tissues (12, 13). Therefore, cathepsins other than Cat B may also be involved in angiogenesis, tumor growth, cell proliferation, and...

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Diminished corneal angiogenesis in gelatinase A‐deficient mice

Cited by 121 publications

References 11 publications

Matrix metalloproteinases and the regulation of tissue remodelling

Matrix metalloproteinases and the regulation of tissue remodelling

Control of matrix metalloproteinase catalytic activity

Cathepsin S Controls Angiogenesis and Tumor Growth via Matrix-derived Angiogenic Factors

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