Sorsby's fundus dystrophy tissue inhibitor of metalloproteinases-3 (TIMP-3) mutants have unimpaired matrix metalloproteinase inhibitory activities, but affect cell adhesion to the extracellular matrix

Yeow, Karen; Kishnani, Narendra S.; Hutton, Mike; Hawkes, Susan P.; Murphy, Gillian; Edwards, Dylan R.

doi:10.1016/s0945-053x(01)00180-9

Cited by 43 publications

(43 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Treatment of the endothelial cells with S100A4 did not affect the expression of TIMP-2, but downregulated the expression of TIMP-1 and TIMP-3, the inhibitors that are most efficient in interaction with MMP-13 (Stamenkovic, 2000;Yeow et al, 2002). Moreover, latent MMP-13 is a substrate for MMP-14, a membrane-bound metalloproteinase, whose expression was also increased in response to S100A4 treatment.…”

Section: Discussionmentioning

confidence: 92%

Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity

et al. 2004

View full text Add to dashboard Cite

S100A4(mts1) protein expression has been strongly associated with metastatic tumor progression. It has been suggested as a prognostic marker for a number of human cancers. It is proposed that extracellular S100A4 accelerates cancer progression by stimulating the motility of endothelial cells, thereby promoting angiogenesis. Here we show that in 3D culture mouse endothelial cells (SVEC 4-10) respond to recombinant S100A4 by stimulating invasive growth of capillary-like structures. The outgrowth is not dependent on the stimulation of cell proliferation, but rather correlates with the transcriptional modulation of genes involved in the proteolytic degradation of extracellular matrix (ECM). Treatment of SVEC 4-10 with the S100A4 protein leads to the transcriptional activation of collagenase 3 (MMP-13) mRNA followed by subsequent release of the protein from the cells. b-Casein zymography demonstrates enhancement of proteolytic activity associated with MMP-13. This observation indicates that extracellular S100A4 stimulates the production of ECM degrading enzymes from endothelial cells, thereby stimulating the remodeling of ECM. This could explain the angiogenic and metastasis-stimulating activity of S100A4(mts1).

show abstract

Section: Discussionmentioning

confidence: 92%

Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Recombinant S156C TIMP-3 generated in NSO myeloma cells has association rate constants for a range of MMPs that are 2-3-fold reduced compared with wild type TIMP-3 (40). However, the decrease in TIMP activity in RPE cells is in contrast to that reported previously with expression in COS-7 and baby hamster kidney cells (10,40). In both of these cell types, high levels of expression of mutant TIMP-3 protein gives rise to dimers, which are not present in our study with RPE cells.…”

Section: Discussionmentioning

confidence: 99%

Expression of Sorsby's Fundus Dystrophy Mutations in Human Retinal Pigment Epithelial Cells Reduces Matrix Metalloproteinase Inhibition and May Promote Angiogenesis

Qi¹,

Ebrahem²,

Yeow³

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Sorsby's fundus dystrophy (SFD) is an autosomal dominant degenerative disease of the macula caused by mutations in the tissue inhibitor of metalloproteinase-3 (TIMP-3) gene. Choroidal neovascularization is a hallmark of this disease, which closely resembles the exudative form of age-related macular degeneration. However, the mechanism by which TIMP-3 mutations induce the disease phenotype in SFD remains unknown. To address this question we established human retinal pigment epithelial cell lines expressing wild type or S156C (Ser 156 changed to cysteine) mutant TIMP-3. S156C TIMP-3 had reduced matrix metalloproteinase (MMP) inhibitory activity in retinal pigment epithelial cells and resulted in increased secretion and activation of gelatinase A and B. The conditioned medium from these cells induced angiogenesis in "in vivo" chick chorioallantoic membrane assays that could be reversed with recombinant wild type TIMP-3. Our data indicate that the choroidal neovascularization in SFD may be a result of increased MMP activity, which could lead to the stimulation of angiogenesis. These results also suggest the potential therapeutic use of TIMP-3 or synthetic MMP inhibitors in this disease.Sorsby's fundus dystrophy (SFD), 1 a fully penetrant, autosomal dominant, degenerative disease of the macula (1), is manifested by symptoms of night blindness or sudden loss of acuity usually in the third to fourth decades of life due to submacular neovascularization (2-5). Clinically, early mid-peripheral drusen and color vision deficits are found (4, 5). SFD is a relatively rare disease, but it has generated significant interest because it closely resembles the exudative or "wet" form of age-related macular degeneration, the most common cause of blindness in the elderly population of the western world. SFD is characterized by accumulation of extracellular deposits (drusen) in Bruch's membrane, the five-layered sheet of connective tissue that separates the retinal pigment epithelium (RPE) from the choriocapillaris (6). The predominant histopathological feature in the eyes of a 63-year-old patient with SFD was a confluent 30-m thick, lipid-containing amorphous deposit found between the basement membrane of the RPE and the inner collagenous layer of Bruch's membrane (6). This is distinct from the basal linear deposits seen in age-related macular degeneration that consist of filamentous fine granular material and may represent a thickened basement membrane of the RPE (6). The subretinal deposits in both SFD and age-related macular degeneration have been shown to be rich in tissue inhibitor of metalloproteinase-3 (TIMP-3) (7,8). A serious complication of SFD is the invasion of the thickened Bruch's membrane by newly formed, thin-walled vessels derived from the choriocapillaris. These vessels grow into the subretinal space causing exudative detachment of the RPE and loss of photoreceptors (5). SFD has been linked with mutations in the TIMP-3 gene (10 -12) with five different missense mutations and a splice site mutation having been identi...

show abstract

“…ECs from passages 2-6 were used for this study. ECs (removed by brief trypsin treatment) were coated on 12-well plates at a density of 25 (29) was subcloned into pEGFP-N1 (Clontech), replacing the enhanced green fluorescent protein cDNA (30). Mouse TACE cDNA in pMOS was a gift from Celltech Chiroscience (Bothell, WA) (28).…”

Section: Methodsmentioning

confidence: 99%

Tumor Necrosis Factor-α-converting Enzyme (TACE/ADAM-17) Mediates the Ectodomain Cleavage of Intercellular Adhesion Molecule-1 (ICAM-1)

Tsakadze

Sithu

Sen

et al. 2006

Journal of Biological Chemistry

Self Cite

152

119

View full text Add to dashboard Cite

Intercellular adhesion molecule-1 (ICAM-1), 3 a cell adhesion molecule expressed in various cell types, plays a key role in mediating the inflammatory and immune responses (1). It functions as a co-stimulatory molecule during antigen presentation to T cells. ICAM-1 interaction with leukocyte integrins LFA-1 and Mac-1 promotes firm adhesion of leukocytes and their transmigration to the sites of inflammation (1-3). ICAM-1 consists of five Ig-like domains, a single transmembrane domain, and a short cytoplasmic tail. ICAM-1 is shed as soluble ICAM-1 (sICAM-1) in blood and other biological fluids. Elevated plasma levels of sICAM-1 have been reported in inflammatory, neoplastic, autoimmune, and vascular diseases (4), and sICAM-1 is utilized as a marker of inflammation and a predictor of prognosis (5, 6). Multiple signaling pathways regulate the shedding of ICAM-1 in 293 cells transfected with ICAM-1 (293 ICAM-1 ), including mitogen-activated protein kinase and phosphatidylinositol 3-kinases (7). How these signaling cascades mediate ICAM-1 release is currently unknown. Previous reports indicate that ICAM-1 is a substrate for matrix metalloprotease (MMP)-9 (8) as well as human leukocyte elastase and cathepsin G (9, 10).Ectodomain shedding is an important regulatory mechanism in the function of membrane-bound cell-surface molecules (reviewed in Refs. 11 and 12). Cytokines and their receptors, growth factors, ectoenzymes, adhesion molecules, and proteoglycans undergo shedding (13-16). The most widely studied inducer of shedding is phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (16, 18 -20). Calcium ionophores, cytokines, growth factors, and chemotactic peptides also induce shedding (22). The majority of the shedding events are mediated by the zinc-dependent metalloproteinases of the metzincin family, which includes MMPs and proteases containing a disintegrin and metalloproteinase (ADAM) domain. Tissue inhibitors of metalloproteinases (TIMPs) regulate the activity of MMPs and some ADAMs. There are four distinct TIMPs. TIMP-1-4 inhibit a wide range of MMPs, whereas TIMP-3 is also an inhibitor of ADAM-17. ADAM-10 is inhibited by TIMP-1 and -3, whereas ADAM-8 and -9 are very poorly inhibited by, and are unlikely to be physiologically regulated by, TIMPs. To date, no ADAM has been shown to be inhibited by TIMP-2. ADAMs are type I transmembrane glycoproteins; and in addition to their proteolytic activity, they also mediate cell adhesion. Tumor necrosis factor-␣ (TNF␣)-converting enzyme (TACE) plays a central role in ectodomain shedding (16). Cell lines derived from TACE-deficient mice (TACE Ϫ/Ϫ ) verify that TACE is involved in the PMA-induced shedding of a number of structurally and functionally diverse proteins, including pro-TNF␣, L-selectin, ␤-amyloid precursor protein, transforming growth factor-␣, heparin-binding epidermal growth factor (EGF), and vascular cell adhesion molecule-1 (VCAM-1) (14, 17-21), suggesting a common shedding mechanism regulated by a protein kinase C-TACE axis. Mice lacking T...

show abstract

Sorsby's fundus dystrophy tissue inhibitor of metalloproteinases-3 (TIMP-3) mutants have unimpaired matrix metalloproteinase inhibitory activities, but affect cell adhesion to the extracellular matrix

Cited by 43 publications

References 45 publications

Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity

Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity

Expression of Sorsby's Fundus Dystrophy Mutations in Human Retinal Pigment Epithelial Cells Reduces Matrix Metalloproteinase Inhibition and May Promote Angiogenesis

Tumor Necrosis Factor-α-converting Enzyme (TACE/ADAM-17) Mediates the Ectodomain Cleavage of Intercellular Adhesion Molecule-1 (ICAM-1)

Contact Info

Product

Resources

About