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See detailInjection de concentrés plaquettaires et régénération tendineuse : modèle animal
Kaux, Jean-François ULg; Drion, Pierre ULg; Renouf, Julien et al

in 3ème Congrès Commun SFMS - SFTS (2010, October 01)

Introduction : La régénération tendineuse en traumatologie du sport demeure un processus actuellement difficile à gérer et de nouvelles voies thérapeutiques sont en cours d’exploration. La littérature ... [more ▼]

Introduction : La régénération tendineuse en traumatologie du sport demeure un processus actuellement difficile à gérer et de nouvelles voies thérapeutiques sont en cours d’exploration. La littérature récente fait état d’effets bénéfiques sur la régénération tendineuse de concentrés plaquettaires (platelet-rich plasma ou PRP), administrés in situ, dus au relargage de facteurs de croissance par activation des plaquettes et à leur activité stimulante au cours de la cicatrisation. Dès lors, nous avons souhaité tester l’effet bénéfique de ce traitement sur des rats préalablement lésés au niveau de leur tendon d’Achille. Matériel et Méthode : Une section unilatérale du tendon d’Achille a été réalisée chez 60 rats Sprague Dawley adultes. De ces 60 rats, 30 ont subi une cicatrisation naturelle (rats contrôles) et 30 rats ont bénéficié d’une injection in situ de PRP le jour de la lésion. Diverses études biomécaniques, biochimiques et histologiques ont été réalisées sur ces tendons d’Achille en cours de cicatrisation à respectivement J5, J15 et J30 après lésion. Dix rats supplémentaires ont servi de témoins sains (sans lésion tendineuse). L’étude biomécanique appréciait la résistance maximale des tendons à la traction à l’aide de mors type « cryo-jaws ». L’étude histologique évaluait l’évolution cellulaire pendant la phase de cicatrisation. L’analyse transcriptomique étudiait l’expression de gènes codant pour le collagène de type III, les métalloprotéases matricielles (MMP-9) et la ténomoduline (TNMD), ainsi qu’un dosage d’hydroxyproline permettant d’évaluer la quantité de collagène présente dans le tendon au cours de la cicatrisation. Résultats : L’étude biomécanique démontre la meilleure résistance des tendons traités avec du PRP par rapport aux tendons contrôles à J5 (+19%), J15 (+30%) et significativement à J30 (+43%). L’étude histologique suggère qu’une injection de PRP stimule la prolifération cellulaire, favorise l’organisation tissulaire, stimule l’angiogenèse et la réorganisation architectural du collagène. L’étude biochimique ne permet pas d’expliquer les effets bénéfiques puisqu’il n’y a pas de différence dans l’expression des gènes des différentes molécules matricielles (collagène de type III, MMP-9 et TNMD) ni dans la quantité d’hydroxyproline qui s’accroit au cours du temps de la cicatrisation de façon similaire dans les deux groupes. Conclusion : L’injection de PRP améliore et accélère la cicatrisation tendineuse et augmente la résistance aux contraintes mécaniques du tendon en cours de cicatrisation. [less ▲]

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See detailLe VEGF-111 comme nouvel outil thérapeutique des lésions tendineuses
Kaux, Jean-François ULg; Drion, Pierre ULg; Libertiaux, Vincent ULg et al

in 3ème Congrès Commun SFMS - SFTS (2010, September 30)

Introduction : Les lésions tendineuses sont très fréquentes en traumatologie du sport et deviennent fréquemment chroniques. Pour ces raisons, de nouvelles thérapeutiques sont en cours de développement ... [more ▼]

Introduction : Les lésions tendineuses sont très fréquentes en traumatologie du sport et deviennent fréquemment chroniques. Pour ces raisons, de nouvelles thérapeutiques sont en cours de développement. Les injections de concentrés plaquettaires (platelet-rich plasma ou PRP) semblent constituer en ce sens une voie encourageante. Elles agissent par libération locale de divers facteurs de croissance parmi lesquels le VEGF-A (vascular endothelial growth factor-A), connu pour induire un effet positif sur la fonction vasculaire et l’angiogenèse, serait impliqué dans le processus cicatriciel des tendons. Récemment, une nouvelle isoforme du VEGF-A a été identifié : le VEGF-111. Celui-ci est une isoforme biologiquement active du VEGF-A, résistant à la protéolyse et aussi connu pour présenter un effet bénéfique sur les pathologies ischémiques. Pour ces raisons, nous avons pensé que le VEGF-111 pourrait avoir un intérêt thérapeutique pour les pathologies tendineuses. Matériel et méthode : 60 rats de souche Sprague-Dawley adultes ont été séparés en 2 groupes (A: groupe contrôle sans traitement et B: groupe traité par une injection de VEGF-111). Chez ces rats, un défaut de 5mm dans le tendon d’Achille a été réalisé après résection du tendon du plantaire grêle. Les 30 rats du groupe B ont alors bénéficié d’une injection in loco de 100ng de VEGF-111. Les rats ont été euthanasiés par groupe de 20 (10 du groupe A et 10 du groupe B) respectivement à J5, J15 et J30 et le tendon d’Achille en cours de régénération a été disséqué et prélevé. Une étude biomécanique de traction jusqu’à rupture a été réalisée à l’aide de mors type « cryo-jaw ». Résultats : L’analyse de nos résultats montre que la force nécessaire pour rompre le tendon lors du test de traction, était plus importante pour les tendons du groupe B. Ces résultats peuvent être observés dès le 5ème jour. Le rapport entre la force et la masse corporelle du rat augmente dans les 2 groupes avec le temps, mais cette augmentation est plus importante pour les tendons du groupe B. La surface de section du tendon de groupe B s’accroit plus rapidement entre les jours 5 et 15 et ensuite se stabilise. Après 30 jours, les sections tendineuses sont similaires dans les 2 groupes. Enfin, dans le groupe B, les contraintes nécessaires pour obtenir la rupture du tendon, en tenant compte de l’accroissement de sa section, sont similaires entre les jours 5 et 15 et augmentent après un mois. Conclusion : Cette expérience a démontré qu’une injection de 100ng de VEGF-111 stimulait le processus de cicatrisation tendineuse en augmentant la résistance du tendon et les contraintes nécessaires pour rompre celui-ci. D’autres expérimentations avec différentes concentrations de VEGF-111 sont actuellement en cours. [less ▲]

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See detailInfluence of the contraction mode on the tendon structure - Rat model
Kaux, Jean-François ULg; Drion, Pierre ULg; Besançon, Benoît et al

in 2nd Congress of European College of Sport & Exercise Physicians - Conference Brochure 2010: Abstracts and CVs (2010, September 09)

Introduction: Tendinopathies are common in sport and affect both upper and lower limbs. Eccentric rehabilitation is a successful way of treating them and now is becoming the “gold treatment”. Although ... [more ▼]

Introduction: Tendinopathies are common in sport and affect both upper and lower limbs. Eccentric rehabilitation is a successful way of treating them and now is becoming the “gold treatment”. Although clinical results are very favorable, beneficial morphological and histological effects have not yet been elucidated. The aim of our experiment was to determine if there exist any intrinsic modifications in a tendon trained in concentric or eccentric modes, in a rat model. Methods: 18 rats were divided into 3 groups: 6 for the control group, without physical restraint; 12 for a training of1 hour, 3 times a week, for 5 weeks, at a speed of 17m/min (1km/h), on a inclined treadmill: 6 rats running uphill at +15° for the concentric effort (group C) and 6 rats running downhill at -15° for the eccentric effort (group E). After this training period, the Achilles, patellar and tricipital tendons of both limbs were surgically removed in all 18 rats. Tendons taken from five rats of each group were subjected to a tensile test up to rupture using a “cryo” jaw. Tendons of the remaining rat of each group were subjected to a histological study. Results: The results showed significant changes in group E only: (1) an increase of the force required to rupture the patellar and tricipital tendons; (2) an improvement of the ratio between the force necessary to rupture the tricipital tendon and the body mass of the rats; (3) an increase of the surface area of the section of the tricipital tendon. No significant change was observed as far as constraint was concerned between groups. Histologically, we saw, in the group E, more peripheral blood vessels and a greater proportion of collagen. Conclusion: This study showed that the mechanical properties of tendon tissue are enhanced by eccentric training. Tendons become stronger, the amount of collagen increases and there is probably more interaction between collagen fibers (mechanotransduction). [less ▲]

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See detailVEGF-111 as a new therapeutic tool for tendon lesion
Kaux, Jean-François ULg; Drion, Pierre ULg; Libertiaux, Vincent ULg et al

in Osteoarthritis and Cartilage (2010, September), 18(Supplement 2), 22

Introduction: Tendon lesion is one of the most frequent pathology in sports and by physical workers. This pathology often becomes chronic. For this reason, it is of interest to develop new treatments ... [more ▼]

Introduction: Tendon lesion is one of the most frequent pathology in sports and by physical workers. This pathology often becomes chronic. For this reason, it is of interest to develop new treatments. Injection of platelet-rich plasma (PRP) seems to be a promising one by releasing growth factors (GF) locally. Among all the GF released by activated platelets, the vascular endothelial growth factor-A (VEGF-A) is known to induce positive effects on vascular function and angiogenesis, and could be implicated in the healing process of tendons. Recently, a novel VEGF-A isoform was identified, the VEGF-111, a biologically active and proteolysis-resistant VEGF-A isoform, also known to present beneficial effects on ischemic diseases. This prompted us to evaluate whether VEFF-111 would have a therapeutic interest within the framework of the tendon pathology. Methods: 60 Rats were divided into 2 groups: A: control (no injection), B: VEGF-111 treatment. A 5mm defect was surgically induced in rat Achilles tendon after resection of plantaris tendon. Rats received a local injection of VEGF-111 (100ng) in situ after the surgery and were placed in their cages without immobilization. After 5, 15 and 30 days, the traumatized Achilles tendons of 10 rats of both groups were removed and dissected during their healing process. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. Rats were then euthanized. Statistical analyses were made with an ANOVA. Values are significant when p-value is below 0.05. Results: Our results shown that the developed force necessary to induce tendon rupture during biomechanical tensile test was greater for tendons which had received an injection of 100ng of VEGF-111. These results were already noticed from day 5 onwards. The ratio between force and weight increased with time in both groups, but this ratio was greater for tendons which had been submitted to an injection of VEGF111. The surface area of the section of the tendons increased between 5 and 15 days followed by a stabilization. After 30 days, sections in both groups were similar. Thus, the constraint was similar after 5 and 15 days but was better for VEGF111 group after one month. Discussion - Conclusion: This experimentation has shown that a 100ng injection of VEGF-111 stimulated tendon healing process as suggested by the increased force needed to break tendons during its healing process and the increased of constraint in comparison with the control group. Other experimentations with different concentration of VEGF111 are now in process. Acknowledgement This experimentation was partially financed by “Standard de Liège 2007” and “Lejeune-Lechien 2008” grants. [less ▲]

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See detailNew use of VEGF in therapeutics: application in tendon lesions
Kaux, Jean-François ULg; Le Goff, Caroline ULg; Drion, Pierre ULg et al

in Clinical Chemistry (2010, July), 56(S6), 111

Introduction: As demonstrated in previous studies, mechanical overload, injury and inflammation, hypoxic condition or any combination of the above could lead to increased expression of VEGF in the tendon ... [more ▼]

Introduction: As demonstrated in previous studies, mechanical overload, injury and inflammation, hypoxic condition or any combination of the above could lead to increased expression of VEGF in the tendon. Thus, VEGF could participate in the healing of pathological tendons. Indeed, some authors are convinced that this neovascularization is the sign of a chronic tendinopathy while others plead in favour of it being a sign of healing processes. The VEGF111, which is a biologically active and proteolysis-resistant VEGF-A isoform, was recently identified. It is induced by ultraviolet B and genotoxic drugs. Experimentation shows that, in nude mice, tumors formed by HEK293 cells expressing VEGF111 develop a more widespread peritumoral neovascularisation than those expressing other VEGF isoforms. Good angiogenic activity and resistance to proteolysis makes VEGF111 a potential beneficial therapeutic option for ischemic diseases. The aim of our study was to determine whether if VEGF111 could have a therapeutic interest in the framework of tendinous pathology. Methods (*): A 5mm defect was surgically induced in Achilles tendon of 60 rats. Rats were divided into 2 groups of 30: A: a control group (no injection) and B: with a VEGF111 injection. The rats of group B received an injection of 100 ng of VEGF111 in situ 1 hour after surgery on the site of the tendon lesion. Afterwards, rats of both groups were placed in their cages without immobilization. After 5, 15 and 30 days, 10 rats of each group were euthanized. The traumatized Achilles tendon of each rat was dissected and removed. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a tensile machine with “Cryo-jaw”. Statistical analyses were made with an ANOVA. Results: A significant increase over time of the force necessary to induce tendon rupture was observed for tendons which had been submitted to an injection of VEGF111 (p=0.016). The force required to break the tendon is always greater for the VEGF111 group (p<0.05). Discussion: We demonstrated that the force necessary to induce the rupture of a rat’s Achilles tendon during biomechanical tensile testing was greater for tendons which had been submitted to an injection of VEGF111. Thus, this experimentation showed that VEGF111 injections could accelerate the tendon healing process and increase the force needed to break tendons in their healing process. Conclusion: VEGF111 could be a new therapy for tendon lesions. However, other experimentation using a rat model with different concentrations of VEGF111 should be made to ascertain the best concentration for this healing process. Acknowledgement: This experimentation was partially financed by “Standard de Liège” and “Lejeune-Lechien” grants. (*) All experimental procedures and protocols used in this investigation were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Liège. [less ▲]

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See detailRole of the netrin-like domain of procollagen C-proteinase enhancer-1 in the control of metalloproteinase activity.
Bekhouche, M.; Kronenberg; Colige, Alain ULg et al

in Journal of Biological Chemistry (2010), 285(21), 15950-9

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See detailComparison between platelet-rich plasma (PRP) and vascular endothelial growth factor-111 (VEGF-111) as a therapeutic tool in tendon healing process
Kaux, Jean-François ULg; Drion, Pierre ULg; Libertiaux, Vincent ULg et al

Poster (2010, March 20)

Introduction In spite of the availability of various treatments for tendinopathy, this pathology often becomes chronic. For this reason, it is of interest to develop new treatments. Among them, the ... [more ▼]

Introduction In spite of the availability of various treatments for tendinopathy, this pathology often becomes chronic. For this reason, it is of interest to develop new treatments. Among them, the injection of platelet-rich plasma (PRP) seems to be a promising one. Indeed, several animal models have demonstrated that injection of blood platelets can initiate and stimulate tendon and ligament repair by releasing growth factors (GF) locally. Among all the GF released by activated platelets, the vascular endothelial growth factor-A (VEGF-A) is known to induce positive effects on vascular function and angiogenesis, and could be implicated in the healing process of tendons. Recently, a novel VEGF-A isoform was identified, the VEGF-111, a biologically active and proteolysis-resistant VEGF-A isoform, also known to present beneficial effects on ischemic diseases. This prompted us to evaluate whether VEFF-111 would have a therapeutic interest within the framework of the tendon pathology. Aim of the study: We hypothesized that the healing of ruptured Achilles tendons, which is the last stage of the Blazina’s classification, could be improved by injection of VEGF-111 that was compared to the potential effect of PRP injections using a rat model. Methods: A 5mm defect was surgically induced in rat Achilles tendon after resection of plantaris tendon. Rats were divided into 3 groups: A: control (no injection), B: PRP treatment and C: VEGF-111 treatment. Rats received a local injection of PRP (50µL) or VEGF-111 (100ng) in situ after the surgery and were placed in their cage without immobilization. After 5, 15 and 30 days, the rats were euthanized in each group. The traumatized Achilles tendon of each rat was removed and dissected during the healing process. Immediately after sampling, tendons were submitted to a biomechanical tensile test up to rupture, using a “Cryo-jaw”. Results: Our results show that developed force necessary to induce tendon rupture during biomechanical tensile test was more important for tendons which had received an injection of PRP or VEGF-111. Moreover, the tensile force necessary to break tendons is higher with PRP than with VEGF-111. These results were already noticed from day 5 onwards. Conclusion: This experimentation has shown that both PRP and VEGF-111 injections stimulated tendon healing process as suggested by the increased force needed to break tendons during its healing process. Furthermore, this acceleration of the cicatrisation process was more significant with PRP than with VEGF-111. This could be explained by the release from platelets of a “cocktail” of growth factors acting in synergy on the healing process. Acknowledgement This experimentation was partially financed by “Standard de Liège 2007” and “Lejeune-Lechien 2008” grants. [less ▲]

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See detailComparison of chitosan/siRNA and trimethylchitosan/siRNA complexes behaviour in vitro
Dehousse, Vincent ULg; Garbacki, Nancy ULg; Jaspart, Séverine ULg et al

in International Journal of Biological Macromolecules (2010), 46

Chitosan and trimethylchitosan (TMC)-siRNA nanoparticles were produced by simple complexation technique or by ionic gelation using tripolyphosphate (TPP). The obtained complexes were characterized in ... [more ▼]

Chitosan and trimethylchitosan (TMC)-siRNA nanoparticles were produced by simple complexation technique or by ionic gelation using tripolyphosphate (TPP). The obtained complexes were characterized in terms of physicochemical properties such as size, zeta potential, complexation efficiency and stability. Furthermore, cytotoxicity, cell uptake and transfection efficiency of polyplexes were evaluated in vitro. Under pH condition of cell culture medium, a strong decrease in siRNA condensation efficiency was observed with chitosan nanoparticles. This characteristic resulted in low transfection efficiencies in HEK293 cell line. Formulation of chitosan polyplexes with TPP led to improvement of polyplexes stability but no significant increase in transfection efficiency was observed compared to simple chitosan complexes. By contrast, TMC complexes did not have pH dependency on siRNA complexation. TMCsiRNA nanoparticles were stable in physiological condition. Accordingly, cellular uptake was increased compared to chitosan polyplexes. However, improvement of transfection efficiency was low regarding to cellular uptake of these complexes. Chitosan and TMC complexes present some characteristics favourable for siRNA delivery, such as ability to integrate siRNA into small discrete particles or low toxicity of the complexes. This study also highlights the importance of complexes stability in physiological environment for siRNA transfection purposes. [less ▲]

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See detailDevelopment of pH–responsive nanocarriers using trimethylchitosans and methacrylic acid copolymer for siRNA delivery
Dehousse, Vincent ULg; Garbacki, Nancy ULg; Colige, Alain ULg et al

in Biomaterials (2010), 31

RNA interference-based therapies are dependent on intracellular delivery of siRNA. The release of siRNA from the endosomal compartment may be a rate limiting step in the transfection process. The purpose ... [more ▼]

RNA interference-based therapies are dependent on intracellular delivery of siRNA. The release of siRNA from the endosomal compartment may be a rate limiting step in the transfection process. The purpose of this study was to produce pH–responsive nanocarriers made of trimethylchitosan (TMC). To this end, pHsensitive methacrylic acid (MAA) copolymer was added to TMC–siRNA formulations. Four different TMCs associated or not with MAA were evaluated as siRNA carriers. Nanoparticles were characterized in terms of size, surface charge, morphology and interaction with siRNA. A swelling behaviour due to a decrease in pH was observed and was found to be dependent on MAA content in the complexes. In vitro experiments aimed at evaluating how the capacity of the nanocarriers to transfect siRNA in L929 cells was affected by MAA content. Confocal microscopy experiments showed that fluorescent MAA-containing particles exhibit a different distribution pattern inside the cells comparing to their counterpart without this pH-sensitive polymer. Transfection efficiency was investigated by RhoA mRNA expression inhibition. MAA–TMC–siRNA complexes were able to transfect L929 cells with greater efficiency than corresponding TMC–siRNA complexes. This study gives an insight into the opportunity of pH-sensitive nanocarriers for siRNA delivery. Such formulations may represent an attractive strategy to improve endosomal escape of siRNA. [less ▲]

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See detailAlternative splicing: a promising target for pharmaceutical inhibition of pathological angiogenesis?
Munaut, Carine ULg; Colige, Alain ULg; Lambert, Charles ULg

in Current Pharmaceutical Design (2010), 16(35), 3864-76

In eukaryotes, genes consist in coding sequences (exons) interspersed with non-coding ones (introns). The regulation of alternative inclusion/exclusion of exons, or part of exons, during the maturation of ... [more ▼]

In eukaryotes, genes consist in coding sequences (exons) interspersed with non-coding ones (introns). The regulation of alternative inclusion/exclusion of exons, or part of exons, during the maturation of the pre-mRNA into mRNA (alternative splicing) allows a dramatic increase of the protein versus the gene repertoire. In a number of cases, alternative splicing decision generates proteins with distinct, sometimes opposite, functions from a given gene. Angiogenesis is the process of vascularisation in physiological conditions and a series of pathologies, including cancer where it favours tumour progression and dissemination of metastasis. In this issue, we discuss some key examples showing how alternative splicing may induce a switch from anti-angiogenic to pro-angiogenic functions and reciprocally. For some of these splicing events, the molecular mechanisms that trigger alternative splicing toward one or the other direction start to be elucidated. The emergence of strategies enabling to regulate alternative splicing opens new routes for anti-angiogenic therapies. [less ▲]

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See detailADAMTS-2 functions as anti-angiogenic and anti-tumoral molecule independently of its catalytic activity.
Dubail, Johanne ULg; Kesteloot, F.; Deroanne, Christophe ULg et al

in Cellular & Molecular Life Sciences (2010)

ADAMTS-2 is a metalloproteinase that plays a key role in the processing of fibrillar procollagen precursors into mature collagen molecules by excising the amino-propeptide. We demonstrate that recombinant ... [more ▼]

ADAMTS-2 is a metalloproteinase that plays a key role in the processing of fibrillar procollagen precursors into mature collagen molecules by excising the amino-propeptide. We demonstrate that recombinant ADAMTS-2 is also able to reduce proliferation of endothelial cells, and to induce their retraction and detachment from the substrate resulting in apoptosis. Dephosphorylation of Erk1/2 and MLC largely precedes the ADAMTS-2 induced morphological alterations. In 3-D culture models, ADAMTS-2 strongly reduced branching of capillary-like structures formed by endothelial cells and their long-term maintenance and inhibited vessels formation in embryoid bodies (EB). Growth and vascularization of tumors formed in nude mice by HEK 293-EBNA cells expressing ADAMTS-2 were drastically reduced. A similar anti-tumoral activity was observed when using cells expressing recombinant deleted forms of ADAMTS-2, including catalytically inactive enzyme. Nucleolin, a nuclear protein also found to be associated with the cell membrane, was identified as a potential receptor mediating the antiangiogenic properties of ADAMTS-2. [less ▲]

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See detailHistological and transcriptional study of angiogenesis and lymphangiogenesis in uninvolved skin, acute pinpoint lesions and established psoriasis plaques: an approach of vascular development chronology in psoriasis
Henno, Audrey ULg; Blacher, Silvia ULg; Lambert, Charles ULg et al

in Journal of Dermatological Science (2010), 57(3), 162-169

Background Dysregulation of angiogenesis and lymphangiogenesis could participate in psoriasis pathogenesis. Analysis of nascent psoriasis lesions should help at identifying early vascular anomalies ... [more ▼]

Background Dysregulation of angiogenesis and lymphangiogenesis could participate in psoriasis pathogenesis. Analysis of nascent psoriasis lesions should help at identifying early vascular anomalies. Objective To analyse vascular development, angiogenesis and lymphangiogenesis markers expression in uninvolved skin in psoriatic patients (N), early psoriasis lesions or pinpoints (PP) and psoriasis plaques (PSO). Methods Skin biopsies were taken in 17 patients in N and in PSO and/or PP. The mRNA steady-state level of angiogenesis and lymphangiogenesis markers was measured by RT-PCR. Immunohistochemistry was performed for von Willebrand factor, podoplanin, Ki-67 and VEGFR3. Blood (BV) and lymphatic (LV) vessels expansion was measured by computer-assisted morphometry. Results Clinical and epidermal aspects indicated that PP are intermediate between N and PSO. While total BV area was already increased in PP similarly to PSO as compared to N, LV area in PP was intermediate between N and PSO. Mean LV size was identical in N and PP and increased in PSO, mean BV size in PP being intermediate between N and PSO. VEGF-A 189 variant was increased in PP as compared to N and PSO. As compared to N, angiogenesis markers (VEGF-A isoforms, PlGF, VEGFR2, NRP-1), VEGF-C and NRP-2 were similarly increased in PP and PSO. Keratin 16 and the lymphangiogenesis markers (VEGFR3, prox-1) were intermediate in PP. Conclusion These data suggest that the expansion of lymphatic vessels occurs after blood vascular development in psoriasis. Expansion of BV in PP could be followed by vessel enlargement during progression to PSO, in parallel with a decreased VEGF-A 189/VEGF-A 121 balance in plaques [less ▲]

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See detailPreparation of cross-linked chitosan-based nanofibers as wound dressing
Aqil, Abdelhafid ULg; Ziani, K.; Tchemtchoua Tateu, Victor ULg et al

Poster (2009, November 18)

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See detailNew asthma biomarkers: lessons from murine models of acute and chronic asthma.
Di Valentin, Emmanuel ULg; Crahay, Céline; Garbacki, Nancy ULg et al

in American Journal of Physiology - Lung Cellular and Molecular Physiology (2009), 296(2), 185-97

Many patients suffering from asthma are not fully controlled by currently available treatments, and some of them display an airway remodeling leading to exaggerated lung function decline. The aim of the ... [more ▼]

Many patients suffering from asthma are not fully controlled by currently available treatments, and some of them display an airway remodeling leading to exaggerated lung function decline. The aim of the present study was to unveil new mediators in asthma to better understand pathophysiology and propose or validate new potential therapeutic targets. A mouse model of asthma mimicking acute or chronic asthma disease was used to select genes undergoing a modulation in both acute and chronic conditions. Mice were exposed to ovalbumin or PBS for 1, 5, and 10 wk [short-, intermediate-, and long-term model (ST, IT, and LT)], and gene expression in the lung was studied using an Affymetrix 430 2.0 genome-wide microarray and further confirmed by RT-PCR and immunohistochemistry for selected targets. We report that 598, 1,406, and 117 genes were upregulated and 490, 153, 321 downregulated at ST, IT, and LT, respectively. Genes related to mucous secretion displayed a progressively amplified expression during the allergen exposure protocol, whereas genes corresponding to growth and differentiation factors, matrix metalloproteinases, and collagens were mainly upregulated at IT. By contrast, genes related to cell division were upregulated at ST and IT and were downregulated at LT. In this study, besides confirming that Arg1, Slc26a4, Ear11, and Mmp12 genes are highly modulated throughout the asthma pathology, we show for the first time that Agr2, Scin, and Cd209e genes are overexpressed throughout the allergen exposure and might therefore be considered as suitable new potential targets for the treatment of asthma. [less ▲]

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See detailThe CORALS project: simulated Cosmic Radiations and Alternative Splicing.
Lambert, Charles ULg; Battout, S.; Van Oostveldt, P. et al

Conference (2009)

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