Exploring the interface between metallo-proteinase activity and growth factor and cytokine bioavailability

Fowlkes, John L.; Winkler, Margaret

doi:10.1016/s1359-6101(02)00005-9

Cited by 75 publications

(40 citation statements)

References 75 publications

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“…Also, the capsule could contain low levels of other, as yet uncharacterized, proteinases with the potential to release these growth factors, which in combination would influence lens cell survival, proliferation, and differentiation (Liu et al, 1996). The bio-context of FGF-2 availability could also influence its effect, because heparan sulfate proteoglycans (HSPGs) that facilitate FGF-2 binding to its receptor (Roghani et al, 1994;Venkataraman et al, 1994;Padera et al, 1999) are also potential substrates for MMP-2 (Fowlkes and Winkler, 2002). HSPs are important components of the lens capsule (Azuma and Hara, 1998) and altering their biosynthesis can cause both lens hypoplasia and anophthalmia (Pan et al, 2006).…”

Section: Lens Epithelial Cell Stress Resistance Requires Mmp-2mentioning

confidence: 99%

“…HSPs are important components of the lens capsule (Azuma and Hara, 1998) and altering their biosynthesis can cause both lens hypoplasia and anophthalmia (Pan et al, 2006). Indeed, MMP-2 is also known to activate latent cytokines, such as IL1-B and TNF-␣ (Fowlkes and Winkler, 2002) and most recently been shown to proteolyse and release E-cadherin, promoting EMT in lens epithelial cells exposed to TGF-␤ (Dwivedi et al, 2006). It can also alter the ECM microenvironment to reveal cryptic proliferative sites in laminin and collagen (Pirila et al, 2003) and generate "matrikines" from processed ECM molecules (Tran et al, 2004).…”

Section: Lens Epithelial Cell Stress Resistance Requires Mmp-2mentioning

confidence: 99%

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FGF-2 Release from the Lens Capsule by MMP-2 Maintains Lens Epithelial Cell Viability

Tholozan

Gribbon

et al. 2007

MBoC

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The lens is an avascular tissue, separated from the aqueous and vitreous humors by its own extracellular matrix, the lens capsule. Here we demonstrate that the lens capsule is a source of essential survival factors for lens epithelial cells. Primary and immortalized lens epithelial cells survive in low levels of serum and are resistant to staurosporine-induced apoptosis when they remain in contact with the lens capsule. Physical contact with the capsule is required for maximal resistance to stress. The lens capsule is also a source of soluble factors including fibroblast growth factor 2 (FGF-2) and perlecan, an extracellular matrix component that enhances FGF-2 activity. Matrix metalloproteinase 2 (MMP-2) inhibition as well as MMP-2 pretreatment of lens capsules greatly reduced the protective effect of the lens capsule, although this could be largely reversed by the addition of either conditioned medium or recombinant FGF-2. These data suggest that FGF-2 release from the lens capsule by MMP-2 is essential to lens epithelial cell viability and survival. INTRODUCTIONCell survival requires the continued exposure to specific survival factors. In a classic study (Ishizaki et al., 1993), lens epithelial cells were shown to survive in culture, in the absence of cell-cell contact, as long as the right growth factor cues were available. These factors could be provided exogenously either in the form of conditioned media or in serum supplement (Ishizaki et al., 1993), leading to the widely accepted general hypothesis that cells are programmed to die unless the appropriate signals are received.The recent proposal of the extracellular matrix (ECM) reservoir hypothesis suggests that the ECM itself can act as a reservoir for growth and survival factors (Bergers et al., 2000;Mott and Werb, 2004) that are released via the action of various matrix metalloproteinases (MMPs; reviewed in McCawley and Matrisian, 2001;Mott and Werb, 2004). MMPs have been shown to release fibroblast growth factor (FGF)-2 (MMP-1, -3; Whitelock et al., 1996) and fibroblast growth factor receptor (FGFR)-1 (MMP-2; Levi et al., 1996), activate transforming growth factor (TGF)-␤1/2 (Yu and Stamenkovic, 2000), and to both activate and release insulin-like growth factor (IGF)-1 (MMP-1, -2, -3, and -9;Fowlkes et al., 1994; and MMP-2, -3, and -7;Imai et al., 1997). MMPs are therefore an essential component in this proposed role for the ECM in cell survival and cell proliferation (Ishizuya-Oka et al., 2000;Wiseman et al., 2003). From such data, we can see that the ECM reservoir hypothesis requires three essential components: an ECM, growth factors sequestered by the ECM, and the presence of MMPs to release the growth factors from the ECM. This hypothesis changes our perception of the ECM as it can no longer be considered to solely provide a physical support or appropriate cues for integrin signaling (Hynes, 1992;Adams and Watt, 1993), but is also a source of cell proliferation and survival factors (Klagsbrun, 1990;Taipale and Keski-Oja, 1997;Bergers et al., 2000;...

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Section: Lens Epithelial Cell Stress Resistance Requires Mmp-2mentioning

confidence: 99%

Section: Lens Epithelial Cell Stress Resistance Requires Mmp-2mentioning

confidence: 99%

FGF-2 Release from the Lens Capsule by MMP-2 Maintains Lens Epithelial Cell Viability

Tholozan

Gribbon

et al. 2007

MBoC

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“…With regard to the second hypothesis, it is known that some growth factors and cytokines are associated with other proteins that can suppress their actions and that in order to activate these factors and cytokines, they must first be liberated from these proteins by proteolytic processing (17)(18)(19). Natural fulllength ANGPTL3 may also be in complex with a protein, and this protein may be bound to the active site of ANGPTL3.…”

Section: Fig 3 Cleavage Of Angptl3 In Vivomentioning

confidence: 99%

Protein Region Important for Regulation of Lipid Metabolism in Angiopoietin-like 3 (ANGPTL3)

Ono

Shimizugawa

Shimamura

et al. 2003

Journal of Biological Chemistry

194

213

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Angiopoietin-like 3 (ANGPTL3) is a secreted protein that is mainly expressed in the liver and regulates lipid metabolism by inhibiting the lipolysis of triglyceriderich lipoproteins. Using deletion mutants of human ANGPTL3, we demonstrated that the N-terminal coiledcoil domain-containing fragment-(17-207) and not the C-terminal fibrinogen-like domain-containing fragment-(207-460) increased the plasma triglyceride levels in mice. We also found that the N-terminal region 17-165 was required to increase plasma triglyceride levels in mice and that a substitution of basic amino acid residues in the region 61-66 of the fragment showed no increase in the plasma triglyceride levels and no inhibition of lipolysis by lipoprotein lipase. In addition, when we analyzed ANGPTL3 in human plasma, we detected cleaved fragments of ANGPTL3. By analyzing recombinant ANGPTL3 in mouse plasma, we found that it was cleaved at two sites, Arg 221 2Ala 222 and Arg 224 2Thr 225 , which are located in the linker region between the coiled-coil domain and the fibrinogen-like domain. Furthermore, a cleavage-resistant mutant of ANGPTL3 was determined to be less active than wild-type ANGPTL3 in increasing mouse plasma triglyceride levels but not in inhibiting lipoprotein lipase activity. These findings suggest that the cleavage of ANGPTL3 is important for the activation of ANGPTL3 in vivo. Angiopoietin-like 3 (ANGPTL3)1 is a secreted protein that is expressed predominantly in the liver (1). ANGPTL3 is structurally similar to angiopoietins (2-4), which are vascular endothelial growth factors. It also has a signal peptide for secretion, a helical domain predicted to form coiled-coils (CCD), and a C-terminal globular fibrinogen-like domain (FLD). Angiopoietins are ligands that bind to the receptor tyrosine kinase Tie2. The FLDs of angiopoietins bind to Tie2, and the CCDs of angiopoietins mediate ligand homo-oligomerization (5). Although ANGPTL3 does not bind to Tie2, it may also induce angiogenesis by binding to integrin ␣ V ␤ 3 (6).We reported that KK/Snk mice (previously, KK/San) had abnormally low plasma lipid levels and identified a mutation in the Angptl3 gene as the cause of the hypolipidemic phenotype of KK/Snk mice (7,8). Injection of recombinant ANGPTL3 or adenoviruses encoding ANGPTL3 resulted in an increase of plasma lipid levels in mice. It has been speculated that ANGPTL3 was capable of inhibiting lipolysis of triglycerides, because an injection of recombinant ANGPTL3 induced a rapid increase in mouse plasma triglyceride levels (9, 10). We further reported that very low density lipoprotein clearance was enhanced in KK/Snk mice and that recombinant ANGPTL3 directly inhibited lipoprotein lipase (LPL) activity in vitro (11). These observations suggest that ANGPTL3 could be involved in the regulation of lipid metabolism by inhibiting LPL activity.Thus, ANGPTL3 seems to be a multifunctional factor that may regulate both lipid metabolism and angiogenesis. The C-terminal FLD of ANGPTL3 was reported to be involved in angiogenesis via binding t...

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“…Fowlkes and Winkler (2002) have recently reviewed how members of the metzincin family (MMPs, adamalysin-related proteinases) affect the availability of growth factors and cytokines. One possibility is that TIMP-1 prevents the degradation of a newly synthesised growth factor by a constitutively active MP, an ADAM for example.…”

Section: Mechanisms Of Timp-1 Actionmentioning

confidence: 99%

Tissue inhibitor of metalloproteinase-1 stimulates proliferation of human cancer cells by inhibiting a metalloproteinase

2004

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TIMP-1, an B30 kDa glycosylated protein found predominantly in extracellular compartments, is involved in the regulation of a variety of developmental, remodelling, and pathological processes. One function of TIMP-1 is to inhibit certain members of a group of extracellular and cell surface enzymes known collectively as metalloproteinases (MP). These include the matrix metalloproteinases and the adamalysin-like disintegrin and metalloproteinases (ADAMs). Additional activities of TIMP-1 include potentiating the activity of erythroid precursors and stimulating proliferation of certain cancer cell lines. Published evidence suggests that the apparent proliferative action of TIMP-1 is independent of its MP-inhibitory activity; however, reports of a cell surface receptor for TIMP-1 have not been confirmed. We have utilised a baculovirus-based system to produce TIMP-1. Data presented here show that TIMP-1 and synthetic hydroxamate (GM6001) MP inhibitors stimulate proliferation and metabolic activity of MDA-MB-435 cancer cells with similar kinetics. An inactive hydroxamate derivative was ineffective. The TIMP-1-induced increase in proliferation and metabolic activity was not the consequence of the inhibition of apoptosis by TIMP-1 in the serum-free medium. These data taken together imply that the mechanism by which TIMP-1 enhances cell growth depends on its ability to inhibit a metalloproteinase, rather than to stimulate a cell surface receptor by a process independent of its MP-inhibitory activity. Inhibitors of extracellular regulated kinase (U0126) and p38 (SB203580), and to a lesser extent the phosphatidylinositol-3-kinase inhibitor LY294002, suppressed the action of TIMP-1. Assays for ERK1/2 and p38 showed that both were activated by TIMP-1 and GM6001. Mechanisms by which TIMP-1 might act to stimulate cell proliferation are described.

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Exploring the interface between metallo-proteinase activity and growth factor and cytokine bioavailability

Cited by 75 publications

References 75 publications

FGF-2 Release from the Lens Capsule by MMP-2 Maintains Lens Epithelial Cell Viability

FGF-2 Release from the Lens Capsule by MMP-2 Maintains Lens Epithelial Cell Viability

Protein Region Important for Regulation of Lipid Metabolism in Angiopoietin-like 3 (ANGPTL3)

Tissue inhibitor of metalloproteinase-1 stimulates proliferation of human cancer cells by inhibiting a metalloproteinase

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