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See detailCdc42 downregulates MMP-1 expression by inhibiting the ERK1/2 pathway.
Deroanne, Christophe ULg; Hamelryckx, Delphine; Ho, Thi Thanh Giang ULg et al

in Journal of Cell Science (2005), 118(Pt 6), 1173-83

The small GTPases of the Rho family are key intermediates in cellular signalling triggered by activated cell-adhesion receptors. In this study, we took advantage of RNA interference (RNAi) using small ... [more ▼]

The small GTPases of the Rho family are key intermediates in cellular signalling triggered by activated cell-adhesion receptors. In this study, we took advantage of RNA interference (RNAi) using small interfering RNAs (siRNAs) to define the roles of the best-characterized members of the RhoGTPase family, RhoA, Rac1 and Cdc42, in the control of MMP-1, MMP-2 and type-I-collagen expression in normal human skin fibroblasts (HSFs). A specific and long-lasting repression, up to 7 days after transfection, of the three GTPases was achieved by transient transfection of specific siRNA. The silencing of Cdc42, but not that of RhoA or Rac1, induced a 15-fold increase in MMP-1 secretion. This upregulation was confirmed at the mRNA level and observed with two different siRNAs targeting Cdc42. Such a regulation was also observed in various human cell lines and was rescued by re-expressing wild-type Cdc42 encoded by a construct bearing silent mutations impeding its recognition by the siRNA. By contrast, MMP-2 and type-I-collagen expression was not affected by the individual silencing of each Rho GTPase. Cytokine protein array, enzyme-linked immunosorbent assays and reverse-transcription PCR measurements revealed that ablation of Cdc42 induced an overexpression of interleukin 8 and MCP-1. Although these cytokines are known to induce the expression of MMP-1, we showed that they were not involved in the Cdc42-mediated upregulation of MMP-1. Silencing of Cdc42 also induced an increased phosphorylation of ERK1/2 and p38 MAP kinase. The use of chemical inhibitors on Cdc42-ablated cells revealed that the upregulation of MMP-1 is dependent on the ERK1/2 pathways, whereas the p38 MAP kinase pathway displayed an inhibitory role. Simultaneous knock-down of two or three Rho GTPases allowed us to demonstrate that the RhoA-ROCK pathway was not involved in this regulation but that the silencing of Rac1 reduced the effect of Cdc42 suppression. These data suggest that, in vivo, when cell/extracellular-matrix interactions via integrins induce cytoskeleton organization, MMP-1 expression is maintained at a low level by Cdc42 via a repression of the Rac1 and ERK1/2 pathways. Therefore, Cdc42 contributes to ECM homeostasis and connective tissue integrity. [less ▲]

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See detailRole of the RhoGTPases in the cellular receptivity and reactivity to mechanical signals including microgravity
Nusgens, Betty ULg; Chometon, G.; Guignandon, Alain et al

in Journal of Gravitational Physiology : A Journal of the International Society for Gravitational Physiology (2005), 12(1), 269-270

The small G proteins of the Rho Family (RhoGTPases) are key operators in the signaling arising from extracellular matrix through integrin receptors and from membrane receptors for soluble ligands. FLight ... [more ▼]

The small G proteins of the Rho Family (RhoGTPases) are key operators in the signaling arising from extracellular matrix through integrin receptors and from membrane receptors for soluble ligands. FLight data show that microgravity affects cell architecture and gene expression leading us to assume that the signaling pathways(s) involving the RhoGTPAses might disturbed in a weightlessness environment. TO test this hypothesis in microgravityu, we created genetically engineered human fibroblasts that will be used in Biolab on the ISS. [less ▲]

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See detailMMP-9 regulates both positively and negatively collagen gel contraction - A nonproteolytic function of MMP-9
Defawe, Olivier D; Kenagy, Richard D; Choi, Chun et al

in Cardiovascular Research (2005), 66(2), 402-409

Objective: Constrictive remodeling accounts for lumen loss in postangioplasty restenosis. Matrix metalloproteinase-9 (MMP-9) has been shown to prevent constrictive remodeling in vivo. To investigate ... [more ▼]

Objective: Constrictive remodeling accounts for lumen loss in postangioplasty restenosis. Matrix metalloproteinase-9 (MMP-9) has been shown to prevent constrictive remodeling in vivo. To investigate potential mechanisms for this observation, we investigated the role of MMP-9 in smooth muscle cell (SMC)-mediated collagen gel contraction, an in vitro model of constrictive remodeling. Methods: Fischer rat SMCs were stably transfected with a construct-expressing rat-MMP-9 under the control of a tetracycline (Tet)-off promoter. SMCs were seeded in type 1 collagen gels (2.4 mg/ml) in the presence or not of tetracycline (1 mu g/ml), and gel contraction was defined as the percentage of retraction of the collagen gel. The depletion of MMP-9 was obtained by using siRNA targeting MMP-9 mRNA or a blocking antibody. Results: Gel contraction was significantly reduced at all times when MMP-9 was overexpressed (Tet-) as compared with the control condition (Tet+). However, MMP-9 depletion of control (Tet+) SMCS (using siRNA or antibody) also inhibited gel contraction. To resolve the apparent discrepancy and determine if MMP-9 exerts a dose-dependent biphasic effect on gel contraction, conditioned medium and purified rat-MMP-9 were prepared. Gel contraction was significantly increased by addition of 0.8 mg/ml of MMP-9, while high concentrations of MMP-9 (>= 100 mg/ml) inhibited contraction. The addition of BB94 and TIMP-1 did not alter the inhibitory or stimulatory effect of MMP-9. Conclusions: Our data Suggest that MMP-9, independent of its proteolytic function, has a biphasic effect on SMC-mediated collagen gel contraction. Understanding the different roles of MMP-9 Should allow the development of better therapeutic strategies for restenotic vascular disease. (c) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. [less ▲]

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See detailMicrogravity-induced matrix remodelling is linked to reduction in tension of human dermal fibroblasts
Guignandon, A.; Lambert, Charles ULg; Réga, Georgette et al

in Journal of Gravitational Physiology : A Journal of the International Society for Gravitational Physiology (2005), 12(1),

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See detailRGDS and DGEA-induced [Ca2+]i signalling in human dermal fibroblasts.
Mineur, Pierre ULg; Guignandon, A.; Lambert, Charles ULg et al

in Biochimica et Biophysica Acta (2005), 1746(1), 28-37

A pulse of short peptides, RGDS and DGEA in the millimolar range, immediately elicits in normal human fibroblasts a transient increase of intracellular Ca2+ ([Ca2+]i). In the present study, we show that ... [more ▼]

A pulse of short peptides, RGDS and DGEA in the millimolar range, immediately elicits in normal human fibroblasts a transient increase of intracellular Ca2+ ([Ca2+]i). In the present study, we show that this [Ca2+]i occurs in an increasing number of cells as a function of peptides concentration. It is specific of each peptide and inhibited at saturating concentration of the peptide in the culture medium. The [Ca2+]i transient depends on signalling pathways slightly different for DGEA and RGDS involving tyrosine kinase(s) and phosphatase(s), phospholipase C, production of inositol-trisphosphate and release of Ca2+ from the cellular stores. GFOGER, the classical collagen binding peptide of alpha1- alpha2- and alpha11-beta1 integrins, in triple helical or denatured form, does not produce any Ca2+ signal. The [Ca2+]i signalling induced by RGDS and DGEA is inhibited by antibodies against beta1 integrin subunit while that mediated by RGDS is also inhibited by antibodies against the alpha3 integrin. Delay in the acquisition of responsiveness is observed during cell adhesion and spreading on a coat of fibronectin for RGDS or collagen for DGEA or on a coat of the specific integrin-inhibiting antibodies but not by seeding cells on GFOGER or laminin-5. This delay is suppressed specifically by collagenase acting on the collagen coat or trypsin on the fibronectin coat. Our results suggest that free integrins and associated focal complexes generate a Ca2+ signal upon recognition of DGEA and RGDS by different cellular pathways. [less ▲]

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See detailCell survival and preservation of siRNA-mediated protein knock-down upon serum-free cryopreservation (-80 degrees C).
Lambert, Charles ULg; Deroanne, Christophe ULg; Servotte, Sandrine et al

in Gravitational and Space Biology Bulletin (2005), 18(2), 103-4

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See detailADAMTS-2, a metalloproteinase containing a disintegrin domain and thrombospondin type I repeats, a new regulator of angiogenesis
Dubail, Johanne ULg; Kesteloot, Frédéric ULg; Motte, Patrick ULg et al

in Journal of Vascular Research (2005), 42(Suppl. 2), 76

Enzymes of the ADAMTS family are closely related to MMPs and ADAMs. They further contain specific domains, such as the “ThromboSpondin type I” (TSP1) repeats able to strongly repress angiogenesis. The ... [more ▼]

Enzymes of the ADAMTS family are closely related to MMPs and ADAMs. They further contain specific domains, such as the “ThromboSpondin type I” (TSP1) repeats able to strongly repress angiogenesis. The primary function of ADAMTS-2 is to process procollagen type I, II, III and V into mature molecules by excising the amino-propeptide. We further hypothesized that it could modulate angiogenesis through its TSP1 repeats. Recombinant ADAMTS-2 induced morphological changes in HUVEC and HMEC cultured on gelatin, collagen and fibronectin. It also significantly reduced their proliferation, attachment and spreading. Similar effects were observed when using inactive ADAMTS-2 mutated at the Zn++-binding catalytic site. ADAMTS-2 did not alter the initial steps of formation of capillary-like structures by HUVEC in vitro. However, these structures appeared more rapidly disrupted in presence of ADAMTS-2 than in control conditions. Immunostaining with monoclonal antibodies against ADAMTS-2 indicate that it is tightly immobilized at the endothelial cell surface by an heparin-sensitive binding. With the aim to identify mechanism(s)leading to the modulation of angiogenesis by ADAMTS-2, we investigated various signalling pathways critical for EC. Phosphorylation status of FAK was not altered by ADAMTS-2 while a downregulation of phosphorylation of p42/44 MAPK was observed. Our data suggest that ADAMTS-2 reduces angiogenesis by regulating endothelial cell adhesion and proliferation, and by alteration of the stability of the capillary-like structures. These effects do not seem to be mediated by an integrin-dependent signaling pathway. Choroidal neovascularization induced in TS2+/+ or TS2-/- mice by LASER burns was used as in vivo model. Several genes involved in the healing and angiogenesis processes (fibrillar collagens, VEGF, TGF, CTGF, …) were not differently regulated in TS2+/+ and TS2-/- mice 5 days after the LASER impact. Wound capillaries visualized by confocal microscopy after FITC-conjugated dextran injection, were significantly increased (p<0,05) in TS2-/- mice suggesting an increased angiogenic response in the KO animals. The results obtained in in vivo and in vitro models indicate that ADAMTS-2 is involved in the control of angiogenesis. Additional investigations are being performed to determine which domain(s) of the molecule is (are) antiangiogenic and to identify the mechanism(s) underlying this regulatory function. [less ▲]

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See detailGradient of proteolytic enzymes, their inhibitors and matrix proteins expression in a ruptured abdominal aortic aneurysm
Defawe, O. D.; Colige, Alain ULg; Lambert, Charles ULg et al

in European Journal of Clinical Investigation (2004), 34(7), 513-514

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See detailIncreased IL-6 and TGF-beta(1) concentrations in bronchoalveolar lavage fluid associated with thoracic radiotherapy
Barthelemy-Brichant, Nicole ULg; Bosquee, Lionel; Cataldo, Didier ULg et al

in International Journal of Radiation, Oncology, Biology, Physics (2004), 58(3), 758-767

PURPOSE: To assess, in lung cancer patients, the effects of thoracic radiotherapy (RT) on the concentrations of transforming growth factor-beta(1) (TGF-beta(1)) and interleukin-6 (IL-6) in the ... [more ▼]

PURPOSE: To assess, in lung cancer patients, the effects of thoracic radiotherapy (RT) on the concentrations of transforming growth factor-beta(1) (TGF-beta(1)) and interleukin-6 (IL-6) in the bronchoalveolar lavage (BAL) fluid. METHODS AND MATERIALS: Eleven patients with lung cancer requiring RT as part of their treatment were studied. BAL was performed bilaterally before, during, and 1, 3, and 6 months after RT. Before each BAL session, the patient's status was assessed clinically using pulmonary function tests and an adapted late effects on normal tissue-subjective, objective, management, analytic (LENT-SOMA) scale, including subjective and objective alterations. The National Cancer Institute Common Toxicity Criteria were used to grade pneumonitis. The TGF-beta(1) and IL-6 levels in the BAL fluid were determined using the Easia kit. RESULTS: The TGF-beta(1) and IL-6 concentrations in the BAL fluid recovered from the irradiated areas were significantly increased by thoracic RT. The increase in TGF-beta(1) levels tended to be greater in the group of patients who developed severe pneumonitis. In the BAL fluid from the nonirradiated areas, the TGF-beta(1) and IL-6 concentrations remained unchanged. CONCLUSION: The observed increase in TGF-beta(1) and IL-6 concentrations in the BAL fluid recovered from the irradiated lung areas demonstrated that these cytokines may contribute to the process leading to a radiation response in human lung tissue. [less ▲]

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See detailChanges in matrix gene and protein expressions after single or repeated exposure to one minimal erythemal dose of solar-simulated radiation in human skin in vivo
Seite, S.; Colige, Alain ULg; Deroanne, Christophe ULg et al

in Photochemistry and Photobiology (2004), 79(3), 265-271

Damage to the skin extracellular matrix (ECM) is the hallmark of long-term exposure to solar UV radiation. The aim of our study was to investigate the changes induced in unexposed human skin in vivo after ... [more ▼]

Damage to the skin extracellular matrix (ECM) is the hallmark of long-term exposure to solar UV radiation. The aim of our study was to investigate the changes induced in unexposed human skin in vivo after single or repeated (five times a week for 6 weeks) exposure to I minimal erythemal dose (MED) of UV solar-simulated radiation. Morphological and biochemical analyses were used to evaluate the structural ECM components and the balance between the degrading enzymes and their physiologic inhibitors. A three-fold increase in matrix metalloproteinase 2 messenger RNA (mRNA) (P < 0.02, unexposed versus exposed) was observed after both single and repeated exposures. Fibrillin 1 mRNA level was increased by chronic exposure (P < 0.02) and unaltered by a single MED. On the contrary, a single MED significantly enhanced mRNA levels of interleukin-la (IL-1alpha), IL-1beta (P < 0.02) and plasminogen activator inhibitor-1 (P < 0.05). Immunohistochemistry demonstrated a significant decrease in Type-I procollagen localized just below the dermal-epidermal junction in both types of exposed sites. At the same location, the immunodetected tenascin was significantly enhanced, whereas a slight increase in Type-III procollagen deposits was also observed in chronically exposed areas. Although we were unable to observe any change in elastic fibers in chronically exposed buttock skin, a significant increase in lysozyme and alpha-1 antitrypsin deposits on these fibers was observed. These results demonstrate the existence of a differential regulation, after chronic exposure compared with an acute one, of some ECM components and inflammatory mediators. [less ▲]

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See detailMECHANICAL STRAIN MODULATES MONOCYTE CHEMOTACTIC PROTEIN-1 AND IL-1BETA EXPRESSION BY CULTURED HUMAN AORTIC SMOOTH MUSCLE CELLS
Defawe, Olivier; Colige, Alain ULg; Deroanne, Christophe ULg et al

in Cardiovascular Pathology (2004), 13(3 suppl), 189

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See detailEffect of ADAMTS-2, a metalloproteinase containing a disintegrin domain and thrombospondin type I repeats, during angiogenesis in vitro and in vivo
Dubail, Johanne ULg; Kesteloot, Frédéric ULg; Motte, Patrick ULg et al

in Angiogenesis (2004), 7(2), 172

Formation of new blood vessels (angiogenesis) is a key step during the development of various pathologies, including cancer. Enzymes of the ADAMTS family are closely related to MMPs and ADAMs. They ... [more ▼]

Formation of new blood vessels (angiogenesis) is a key step during the development of various pathologies, including cancer. Enzymes of the ADAMTS family are closely related to MMPs and ADAMs. They further contain specific domains, such as the ‘‘Thrombospondin type I’’ (TSP1) repeats, that are able to strongly repress angiogenesis, as described for thrombospondin-1 and -2, and for ADAMTS-1 and -8. The primary function of ADAMTS-2 is to process collagen type I, II and III precursors into mature molecules by excising the aminopropeptide. We further hypothesized that it could modulate angiogenesis through its TSP1 repeats. This hypothesis was investigated using different in vitro experimental models of angiogenesis. Recombinant ADAMTS-2 induced morphological changes in human umbilical vein endothelial cells (HUVEC) and human microvessel endothelial cells (HMEC), and significantly reduced their proliferation, attachment and spreading. Similar effects were observed when using inactive ADAMTS-2 mutated at the Zn2+-binding catalytic site. ADAMTS-2 did not alter the initial steps of formation of capillary-like structures by HUVEC in vitro. However, these structures appeared much less stable and were more rapidly disrupted in presence of ADAMTS-2 than in control conditions. ADAMTS-2 was also tested in an ex vivo angiogenesis model using aortic rings from rats and mice, wild type or KO for ADAMTS-2. Outgrowth of capillaries was slightly increased from aortas of ADAMTS-2 KO mice (TS2-/-) as compared to aortas from control animals (TS2+/+), while addition of full size recombinant ADAMTS-2 reduced the formation of capillary structures from rat aortas, suggesting its anti-angiogenic activity. Choroidal neovascularization induced in TS2+/+ or TS2-/- mice by LASER burns was used as in vivo model to confirm the in vitro and ex vivo results. Several genes involved in the healing and angiogenesis processes (fibrillar collagens, VEGF, TGF-beta and CTGF) were not differently regulated in TS2+/+ and TS2-/- mice at 5 days. [less ▲]

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See detailNovel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (Type VIIC) and common polymorphisms in the ADAMTS2 gene.
Colige, Alain ULg; Nuytinck, Lieve; Hausser, Ingrid et al

in The Journal of investigative dermatology (2004), 123(4), 656-63

Ehlers-Danlos syndrome (EDS) type VIIC, or dermatosparactic type, is a recessively inherited connective tissue disorder characterized, among other symptoms, by an extreme skin fragility resulting from ... [more ▼]

Ehlers-Danlos syndrome (EDS) type VIIC, or dermatosparactic type, is a recessively inherited connective tissue disorder characterized, among other symptoms, by an extreme skin fragility resulting from mutations inactivating ADAMTS-2, an enzyme excising the aminopropeptide of procollagens type I, II, and III. All previously described mutations create premature stop codons leading to a marked reduction in the level of mRNA. In this study, we analyzed the ADAMTS2 cDNA sequences from five patients displaying clinical and/or biochemical features consistent with a diagnosis of either typical or potentially mild form of EDS type VIIC. Three different alterations were detected in the two patients with typical EDS type VIIC. The first patient was homozygous for a genomic deletion causing an in-frame skipping of exons 3-5 in the transcript. In the second patient, the allele inherited from the mother lacks exon 3, generating a premature stop codon, whereas the paternal allele has a genomic deletion resulting in an in-frame skipping of exons 14-16 at the mRNA level. Although the exons 3-5 or 14-16 encode protein domains that have not been previously recognized as crucial for ADAMTS-2 activity, the aminoprocollagen processing was strongly impaired in vitro and in vivo, providing evidence for the requirement of these domains for proper enzyme function. The three other patients with a phenotype with some resemblance to EDS type VIIC only had silent and functionally neutral variations also frequently found in a normal population. [less ▲]

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See detailInvasion and MMP expression profile in desmoid tumours.
Denys, H.; De Wever, O.; Nusgens, Betty ULg et al

in British Journal of Cancer (2004), 90(7), 1443-9

Desmoid tumours are locally invasive soft tissue tumours in which beta-catenin mediated TCF-dependent transcription is activated. The role of soluble factors secreted by the myofibroblastic desmoid tumour ... [more ▼]

Desmoid tumours are locally invasive soft tissue tumours in which beta-catenin mediated TCF-dependent transcription is activated. The role of soluble factors secreted by the myofibroblastic desmoid tumour, which could stimulate tumour invasiveness, was investigated. Using collagen gel invasion assays, the presence of factors stimulating invasion in desmoid conditioned media (CM) could be established. Since matrix metalloproteinases (MMPs) have been implicated in the process of tumoral invasion, the expression levels of the MMP family members were evaluated. Quantitative reverse transcription-PCR was used to determine the expression levels of MMP1, MMP2, MMP3, MMP7, MMP11, MMP12, MMP13, MMP14 and the inhibitors TIMP1, TIMP2 and TIMP3. Besides overexpression of MMP7, a known TCF-dependent target gene, a striking upregulation of the expression levels of MMP1, MMP3, MMP11, MMP12 and MMP13 in desmoid tumours, compared to unaffected fibroblasts from the same patients, was found. Treating the CM of desmoids with a synthetic and a physiologic MMP inhibitor reduced the invasion-stimulating capacity of the desmoid CM by approximately 50%. These results suggest the involvement of soluble factors, released by the desmoid cells, in stimulating invasion and implicate the MMPs as facilitators of invasion. [less ▲]

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See detailThe natural history, including orofacial features of three patients with Ehlers-Danlos syndrome, dermatosparaxis type (EDS type VIIC).
Malfait, Fransiska; De Coster, Peter; Hausser, Ingrid et al

in American Journal of Medical Genetics. Part A (2004), 131(1), 18-28

Ehlers-Danlos syndrome (EDS) dermatosparaxis type (type VIIC) and the related disease of cattle dermatosparaxis, are recessively inherited connective tissue disorders, caused by a deficient activity of ... [more ▼]

Ehlers-Danlos syndrome (EDS) dermatosparaxis type (type VIIC) and the related disease of cattle dermatosparaxis, are recessively inherited connective tissue disorders, caused by a deficient activity of procollagen I N-proteinase, the enzyme that excises the N-terminal propeptide in procollagen type I, type II, and type III. Although well documented in cattle, to date only seven human cases have been recorded, most of them aged under 2 years. We document the natural history of three patients with EDS dermatosparaxis type, two of whom have been reported before the age of 2 years, and one new patient. The phenotype of the patients, and especially the facial resemblance, is striking, making this a clinically recognizable condition. The most consistent anomalies during the first years of life are premature rupture of the membranes, extreme skin fragility and easy bruising, large fontanels, blue sclerae, puffy eyelids, micrognathia, umbilical hernia, and short fingers. Joint hypermobility becomes more important with age. The children are at risk for rupture of internal organs due to soft tissue fragility, as is illustrated by different internal events in two of the three patients described here. Orofacial features include micrognathia, a frontal open bite, and gingival hyperplasia with varying degrees of hyperkeratosis. The deciduous dentition shows abnormal morphology of the molars, obliteration of the tooth pulp, and severe enamel attrition. The permanent dentition shows agenesis and microdontia of several teeth. Tooth discoloration, dysplastic roots, and tooth pulp obliteration are present in a restricted number of permanent teeth. [less ▲]

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See detailEvaluation of the function of ADAMTS-2, a metalloproteinase containing a disintegrin domain and thrombospondin type I repeats, during angiogenesis in vitro and in vivo
Kesteloot, Frédéric ULg; Lapière, Charles M; Colige, Alain ULg et al

in Acta Clinica Belgica (2004), 59(2), 120

Angiogenesis is required for development, growth, tissue remodeling, and wound healing. Pathologies such as diabetic retinopathy, rheumatoid arthritis and cancer would benefit from therapies controlling ... [more ▼]

Angiogenesis is required for development, growth, tissue remodeling, and wound healing. Pathologies such as diabetic retinopathy, rheumatoid arthritis and cancer would benefit from therapies controlling and reducing angiogenesis. Enzymes of the ADAMTS family are closely related to MMPs and ADAMs. They contain however some specific features, such as a variable number of domains known as “ThromboSpondin type I repeat” (TSPI). ADAMTS-1 and -8 are 20-fold more anti-angiogenic than angiostatin and endostatin, two potent inhibitors of angiogenesis. The primary function of ADAMTS-2 is the maturation of collagen type I and II molecules by excising the amino-propeptide. In addition, ADAMTS-2 could also modulate angiogenesis, as it contains the same sequences than those responsible for the anti-angiogenic activity of ADAMTS-1 and -8. This hypothesis was investigated in vitro in different experimental models such as cell proliferation and formation of capillary structures by human endothelial cells. An ex vivo angiogenesis model was also used. It consists in mice or rat aorta pieces embedded in a collagen gel in order to allow the growth of capillaries from the vascular endothelium. As compared to control mice (TS2+/+), angiogenesis was slightly increased, in absence of ADAMTS-2, from aortas of ADAMTS-2 KO mice (TS2-/-). Using rat aortas, addition of recombinant ADAMTS-2 reduced the formation of capillary structure, also confirming the anti-angiogenic activity of ADAMTS-2. Finally, an in vivo model of angiogenesis was also used. Biocompatible sponges (Ivalon) were implanted under the skin of TS2+/+ or TS2-/- mice in order to evaluate the formation of capillaries in the granulation tissue invading the sponge. In absence of ADAMTS-2, angiogenesis and granulation tissue formation were both reduced. Additional investigations are being performed in order to identify the underlying mechanism(s) inducing these modifications. [less ▲]

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See detailDesign and evaluation of new hydrogels for biomaterial purposes
Grandfils, Christian ULg; Barakat, I; Fairon, N et al

Conference (2003, October 23)

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See detailDesign and evaluation of new reinforced hydrogel membranes for biomaterial purposes
Fairon, N; Grandfils, Christian ULg; Barakat, I et al

Poster (2003, October 23)

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See detailIncreased Mrna Expression of Decorin in the Prolapsing Posterior Leaflet of the Mitral Valve
Radermecker, M. A.; Limet, Raymond ULg; Lapiere, C. M. et al

in Interactive Cardiovascular and Thoracic Surgery (2003), 2(3), 389-94

To improve our understanding of myxomatous degeneration of the valvar tissue as seen in mitral valve prolapse, we have compared the biosynthetic phenotype of the connective tissue cells in myxomatous ... [more ▼]

To improve our understanding of myxomatous degeneration of the valvar tissue as seen in mitral valve prolapse, we have compared the biosynthetic phenotype of the connective tissue cells in myxomatous segments (n=4) resected during surgery with that of homologous segments of normal valves (n=4) harvested in age-matched organ donors. The steady-state level of mRNA for selected extracellular matrix macromolecules and metalloproteinases was assessed by quantitative (internal standard controlled) reverse transcriptase-polymerase chain reaction (RT-PCR). Among the investigated gene products, the decorin mRNA expression was significantly increased in degenerative valve compared with normal tissue (211+/-48 vs. 100+/-70, p<0.02). The level of fibrillin 2 also tended to be increased (194+/-88 vs. 100+/-81, p=0.08). These results suggest that myxomatous valvar tissue is characterized by an overexpression of mRNA for decorin. Owing to the role of this small leucine-rich proteoglycan in the regulation of fibril assembly and stability, this alteration may account for or is a result of a defective organization of the collagen and elastic fibers in this disease and contribute to the intrinsic distensibility and fragility of the myxomatous tissue. [less ▲]

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