WorldCat Identities

Moali, Catherine

Overview
Works: 14 works in 15 publications in 2 languages and 20 library holdings
Roles: Other, Thesis advisor, Author, Opponent
Publication Timeline
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Most widely held works by Catherine Moali
Etude de l'oxydation et de la reconnaissance d'analogues d'arginine par les no synthases : Synthèse et caracterisation de nouveaux substrats et inhibiteurs by Catherine Guedes-Moali( Book )

2 editions published in 1999 in French and held by 3 WorldCat member libraries worldwide

Nitric oxide (NO) is a unique biological messenger in mammals. It is produced from L-arginine by hemeproteins called NO synthases (NOS). To get further insight into the mechanism of its biosynthesis, we synthesized a dozen amino-acids bearing a guanidine, hydroxy-guanidine, amidine or amidoxime function and assayed them for their ability to produce nitrogen oxides derived from NO (nitrite and nitrate) in the presence of purified NOS I and II. Thus, we showed that only two new compounds produced NO by a reaction similar to arginine oxidation (monooxygenase activity). A wider set of molecules bearing a C=NOH function were found to be nitrite precursors in the presence of NOS but the reaction proceeded outside the active site, with ten-times lower yields. These compounds were oxidized by the superoxide ion produced by the oxidase activity of NOS. On the other hand, we measured the binding constants of the amino-acids for NOS I and II and demonstrated that two nitrogens, well-positioned relative to the amino-acid moiety, were necessary to allow compounds to bind and be processed by the monooxygenase activity of NOS. Also, this study helped us to understand the role played by the cofactor tetrahydrobiopterin in controlling substrate positioning and NOS activity. These results were used to design new potential inhibitors of NOS
<> by Philipp Arnold( )

1 edition published in 2016 in English and held by 2 WorldCat member libraries worldwide

<> by Frédéric Delolme( )

1 edition published in 2014 in English and held by 2 WorldCat member libraries worldwide

Interaction of Complement Defence Collagens C1q and Mannose-Binding Lectin with BMP-1/Tolloid-like Proteinases by Monique Lacroix( )

1 edition published in 2017 in English and held by 2 WorldCat member libraries worldwide

Degradome of soluble ADAM10 and ADAM17 metalloproteases by Franka Scharfenberg( )

1 edition published in 2019 in English and held by 2 WorldCat member libraries worldwide

Étude protéomique, cellulaire et moléculaire des fonctions de la métalloprotéase BMP-1 dans le contexte de la cicatrisation cornéenne by Maya Talantikite( )

1 edition published in 2017 in French and held by 1 WorldCat member library worldwide

When the cornea is injured, a complex multi-step healing process is triggered which aims at restoring corneal integrity, structure and transparency. However, in some cases, corneal healing results in the formation of a stable scar associated with a prolonged loss of corneal transparency and with functional blindness. The mechanisms involved in the formation of these persistent scars are still not fully understood but it is known that the composition and organization of the extracellular matrix significantly contributes to the maintenance of corneal transparency. This work focused on the extracellular metalloproteinase called BMP-1 (Bone Morphogenetic Protein 1), a major player in the control of extracellular matrix assembly and TGF-beta activation, which was previously shown to be up-regulated in corneal healing and scarring. In order to further probe BMP-1 functions in corneal healing, we first performed a systematic comparison of known or potential BMP-1 inhibitors from different origins to characterize their properties both in vitro and in cell cultures. We then carried out an in-depth study of the secretome of human corneal stromal cells (keratocytes) and of the consequences of the differentiation of these cells into myofibroblasts. Finally, we analyzed BMP-1-mediated proteolytic events in keratocyte secretomes, mainly using a quantitative proteomic approach based on iTRAQ labeling of proteins (TAILS technique). The comparison of BMP-1 available inhibitors revealed different profiles of efficacy, specificity and toxicity and led to the identification of one hydroxamate inhibitor and one protein inhibitor, which were very efficient, non-toxic and very specific of BMP-1. The keratocyte secretome was shown to be a suitable model for the study of BMP-1 activities in the corneal context. More than 2022 proteins were identified, including the BMP-1 metalloprotease and 16 of its 33 already known substrates. Finally, 76 proteins modified by BMP-1 activity were identified in the keratocyte secretome. These results confirm the strong links between BMP-1, extracellular matrix assembly and TGF-beta, but also suggest new roles for this protease in cell proliferation and inflammation. Some of the newly identified substrates (TGFBI, HSP47 and collagen VI) are highly relevant in the context of corneal healing and were validated at the biochemical standpoint. In conclusion, BMP-1 is confirmed as a potential target to treat or prevent the formation of corneal opacities and the characterization of available inhibitors opens up important perspectives for preclinical studies in animals
Etude structure/fonction des interactions de C1q avec des récepteurs de type immunoglobuline impliqués dans la tolérance immune et l'auto-immunité by Guillaume Fouët( )

1 edition published in 2021 in English and held by 1 WorldCat member library worldwide

La molécule C1q a longtemps été étudiée pour son rôle majeur dans l'activation de la voie classique du complément. C1q peut reconnaître de nombreux motifs à la surface des pathogènes ou du soi altéré, via ses six régions globulaires C-terminales (GR). L'autre partie de la protéine, les régions collagéniques (CLR) de C1q, sont généralement associées au tétramère de protéases C1r et C1s (C1r2s2), responsable de l'initiation de la cascade du complément. Ces dernières années, des interactions de C1q avec de nombreux récepteurs membranaires ont été mises en évidence. Parmi ces fonctions indépendantes du complément, un rôle de modulation de la réponse immune par C1q est médié par son interaction avec des récepteurs à domaines de type immunoglobuline (Ig-like) : RAGE (receptor for advanced glycation end-products), CD33, LAIR-1 (leukocyte-associated Ig-like receptor 1) et LAIR-2. Ces récepteurs ont des activités opposées sur les signaux inflammatoires : RAGE induit des signaux pro-inflammatoires alors que CD33 et LAIR-1 sont des récepteurs anti-inflammatoires. Les signaux induits par l'interaction de C1q dépendent donc des récepteurs mis en jeu. Des études récentes suggèrent que RAGE et CD33 interagissent avec les GR alors que LAIR-1 reconnaît les CLR de C1q, ce qui génère un réseau d'interactions complexe qui module la réponse immune en regroupant des signaux pro- et anti-inflammatoires. Cette thèse a pour but d'élucider les détails moléculaires de l'interaction de C1q avec ces récepteurs afin d'aider à la compréhension de la modulation de la réponse immune par C1q. Nous nous sommes principalement intéressés à l'interaction de C1q avec LAIR-1. Une stratégie de dissection moléculaire de C1q, couplée à des expériences de compétition ainsi que l'utilisation de variants de C1q nous ont permis de localiser le site d'interaction de LAIR-1 proche mais différent de celui de C1r2s2 sur les CLR de C1q. Du côté de LAIR-1, une analyse par mutagénèse dirigée nous a permis d'identifier les acides aminés impliqués dans l'interaction avec C1q. Ces résultats suggèrent un modèle d'interaction de C1q avec le domaine Ig-like de LAIR-1. De plus, l'interaction spécifique de LAIR-1 avec les CLR de C1q nous a incité à développer la première production recombinante de cette région de C1q (CLR_nc2). Le remplacement des GR de C1q par le deuxième domaine non collagénique du collagène IX nous a permis de contrôler la mise en registre spécifique des chaînes collagéniques de C1q. La protéine CLR_nc2 a constitué un outil important dans le cadre de cette thèse et le sera certainement également pour l'étude future de l'interaction de C1q avec ses nombreux récepteurs
De la maturation des collagènes à la régulation de la signalisation TGF-ß : nouveaux rôles moléculaires et cellulaires de la métalloprotéase BMP-1 by Cyril Anastasi( )

1 edition published in 2016 in French and held by 1 WorldCat member library worldwide

La Bone Morphogenetic Protein-1 (BMP-1) est une métalloprotéase impliquée dans la maturation et l'activation de nombreuses molécules extracellulaires. Parmi celles-ci, on trouve notamment les collagènes fibrillaires, les protéines les plus abondante chez l'Homme, ainsi que les facteurs de croissance de la superfamille du TGF-ß, des protéines pléiotropes. Au travers de ses fonctions, BMP-1 joue un rôle crucial au cours du développement embryonnaire mais également durant les processus physiologiques et pathologiques de remodelage tissulaire (cicatrisation, fibroses, croissance osseuse, cancers...).Le projet présenté dans ce manuscrit a consisté à étudier plusieurs fonctions importantes de BMP-1 au niveau moléculaire et à caractériser les conséquences de ces activités au niveau de plusieurs types cellulaires.Dans un premier temps, un test quantitatif a été mis au point afin de pouvoir étudier en temps réel l'effet de BMP-1 sur les collagènes fibrillaires ainsi que les mécanismes de sa régulation. Par la suite, de nouveaux substrats de BMP-1 ont été mis en évidence, parmi lesquels des co-récepteurs du TGF-ß (Bétaglycan, CD109) ainsi qu'une protéine matricellulaire (TSP-1). L'étude de ces activités a permis de caractériser les multiples voies par lesquelles BMP-1 est capable de réguler l'activité du facteur de croissance TGF-ß.De plus, nous avons mis en évidence que le clivage de ces différents substrats entraine une modulation importante du phénotype de plusieurs lignées cellulaires (HT1080, HEK-293T) avec des effets au niveau de l'adhésion, la prolifération et la migration cellulaire. En conclusion, ce travail révèle que les activités de BMP-1 s'étendent bien au-delà de ce qui est actuellement décrit
Régulation de l'activité des métalloprotéases Tolloïdes par les protéines à domaine Frizzled by Cécile Bijakowski( )

1 edition published in 2012 in French and held by 1 WorldCat member library worldwide

Tolloid proteinases constitute a group of extracellular metalloproteinases which includes four members in mammals (BMP-1, mTLD, mTLL-1, mTLL-2). These proteinases play major roles in development, tissue repair and related pathological conditions such as fibrosis. In 2006, the first endogenous inhibitor of Tolloid proteinases was identified in Xenopus and zebrafish. This inhibitor, called Sizzled, is a member of the secreted Frizzled- related proteins (sFRPs). The present study strongly suggests that inhibition of Tolloid proteinases activity by sFRPs is not conserved in mammals. Indeed, three of the five mammalian sFRPs were tested (sFRP1, sFRP2 and sFRP4) and none of them was found to inhibit human BMP-1 activity in vitro. In contrast, this study demonstrates that Xenopus Sizzled is a potent and specific inhibitor of human BMP-1, mTLD and mTLL-1. This inhibition involves an interaction between the Frizzled domain of Sizzled and the catalytic domain of Tolloid proteinases. More precisely, residues Asp-92, Phe-94, Ser-43 and Glu-44 of Sizzled (among which only Asp-92 is conserved in mammalian sFRPs) play a crucial role in Tolloid proteinase inhibition. Finally, we studied the longest isoform of collagen XVIII, which also contains a Frizzled domain. We found that BMP-1 can cleave collagen XVIII in vitro, resulting in a Frizzled domain-Containing fragment. Experiments are in progress to determine if this fragment can also inhibit Tolloid proteinase activity
Interaction of complement defence collagens C1q and MBL with BMP-1/tolloid-like proteinases( )

1 edition published in 2017 in English and held by 1 WorldCat member library worldwide

Structuration en 3D de phases cristal-liquides pour la formation biomimétique de tissus osseux by Elora Bessot( )

1 edition published in 2020 in French and held by 1 WorldCat member library worldwide

L'os est un matériau hybride qui associe une trame organique dense et organisée de fibrilles de collagène et un réseau minéral d'hydroxyapatite. La formation de ce matériau hiérarchisé a été souvent étudié biologiquement. Comment l'étudier d'un point de vue physico-chimique et ainsi pouvoir reproduire l'organisation à l'échelle suprafibrillaire ? Nous proposons d'identifier ces paramètres en appliquant in vitro des contraintes aux mésophases du collagène afin de contrôler l'arrangement spatial 3D des domaines orientés. Des chambres microfluidiques mimant l'os compact et des procédés d'émulsion mimant l'interaction os spongieux-moelle osseuse ont été utilisés. Ces modèles ont permis de mettre en évidence l'implication, notamment, du confinement, du flux en collagène et de la géométrie du réseau dans l'organisation fibrillaire résultante. Les techniques de microscopies révèlent que ces organisations biologiques sont issues de la texturisation des mésophases du collagène à l'échelle macroscopique grâce à l'observation de défauts inhérents à la géométrie des tissus. Cette étude ouvre des perspectives dans la compréhension des mécanismes physico-chimiques et l'organisation des domaines anisotropes in vivo intervenant dans la morphogénèse et la biominéralisation. Elle ouvre des perspectives pour l'ingénierie tissulaire afin de réparer de larges défauts et favoriser l'ostéoinduction
Evaluation des effets et du devenir de xénobiotiques dans un contexte d'administration orale par l'utilisation de méthodes alternatives in vitro by Aurélie Loussouarn( )

1 edition published in 2021 in French and held by 1 WorldCat member library worldwide

Xenobiotics are all molecules that are foreign to the human organism and to which it will be exposed during its life. To protect itself from their potential harmful effects, the body is equipped with biological barriers. When xenobiotics enter the body orally, the intestinal barrier is the most impacted. Our objective is to use simple and reproducible in vitro models to evaluate the behaviour of xenobiotics on the intestinal barrier. The first part of this study focused on the behaviour of therapeutic barrier targeting protein (affitin) in the digestive tract. First, synthetic models reproducing gastric and intestinal fluids were used to test its resistance to physicochemical constraints. Protein engineering tools have allowed us to modify the affitin to fight more efficiently against the extreme conditions of the oral route. The second part of the project focused on xenobiotics in drinking waters. The action of different herbicides was tested on a model of the intestinal barrier reproduced with a differentiated Caco-2 cell line. As cellular permeability is a key element in intestinal homeostasis, further investigation was carried out on cell junction proteins. With increasing exposures to xenobiotics, there is a rising interest in identifying their deleterious or non-deleterious effects on human health. Our work highlights that alternative in vitro methods are excellent approaches to extrapolate from in vivo situations. They allow us to study the impacts of xenobiotics on our organism, in a predictive and rapid manner, and without the use of animal experimentation
Electrical impedance spectroscopy applied to the chronic monitoring of the fibrosis induced by cardiac active implants by Amelie Degache( )

1 edition published in 2019 in English and held by 1 WorldCat member library worldwide

Cardiac arrhythmias represent about 50% of the cardiovascular diseases which are the first cause of mortality in the world. Implantable medical devices play a major role for treating these cardiac arrhythmias. In France, about 250.000 patients are equipped with an implanted device for arrhythmia treatment and need a regular monitoring. These devices use the latest technology of micro-nano-electronics and integrate a subcutaneous pulse generator connected to electrodes placed into the heart via intravenous leads. One of the main weaknesses of every implantable device lies in the electrode-tissue interface due to a sustained inflammatory response called fibrosis. This phenomenon jeopardizes the device biocompatibility, because it encapsulates the stimulation lead with an “insulating” tissue, creating adherences along the lead and often leading to an increase of the stimulation threshold over time and a larger electrical consumption. This response is well-known and minimized during the implantation surgery thanks the use of steroid-elution electrodes, however fibrosis still remains an impediment even for the most recent devices, enhancing the interest of studying long-term biocompatibility of cardiac implanted devices.The understanding of fibrosis mechanisms is essential for this work. It consists in some cardiac cells activation and differentiation under a mechanical stress, inducing fibrosis initiation and modifying locally the active cardiac tissue. To characterize this modification, we use electrical impedance measurements, consisting in sending a sinusoidal electrical current I and then measuring the resulting voltage U in the tissue; the impedance Z is the U/I ratio. Depending on the frequency of the measurement signal, we can explore the tissue from the microscopic to the macroscopic scales. As a patient is already equipped with cardiac leads connected to a stimulation device which can also record the cardiac electrical activity, the main idea of this work is to investigate the use of an electrical measurement that could characterize the fibrotic lead encapsulation, with the final objective to embed this characterization method in the implanted circuit. This brings us to the main question of our project: does the fibrosis developing around the cardiac leads have an electrical signature?My thesis work is organized along three axes. Two experimental axes are conducted at cellular and tissue levels, on in vitro or ex vivo models. In addition, an axis studying the feasibility of embedded impedance measurement for in vivo mimicking conditions is also discussed. The ex vivo part presents the characterization of tissue of different natures, healthy or collagenous, it was developed with the IHU LIRYC laboratory, on porcine or ovine cardiac tissue (ventricles mainly), with stimulation electrodes used on patients The impedance spectra are analyzed using a known electrical model from which characteristic parameters of the two tissue types are extracted. After statistical analysis, these parameters are found to be significantly different allowing us to distinguish both tissue types. The in vitro part presents the electrical characterization, using impedance measurements, in parallel to the biological characterization, using immunocytochemistry, of a cellular fibrosis model. It consists in culturing human cardiac cells, activated or not by a growth factor. After a statistical analysis, the impedance values show a significantly different signature for cultures with growth factor, with respect to sham cultures, while the biological characterization confirmed the presence of more activated and differentiated cells over time. The last axis gives preliminary results of embedded impedance measurements in custom circuits
Procollagen C-Proteinase Enhancers in skin wound healing : expression, functions and therapeutic potential by Agnès Tessier( )

1 edition published in 2018 in English and held by 1 WorldCat member library worldwide

The imbalance between collagen assembly and degradation during skin wound healing is a major factor contributing to wound healing pathologies. Fibrillar collagen precursors are synthesized by fibroblasts and processed in the extracellular space by specific metalloproteases (e.g. BMP-1/Tolloid-like Proteinases, or BTPs) to form collagen fibrils. These proteolytic maturations can be efficiently stimulated by two glycoproteins, Procollagen C-Proteinase Enhancers (PCPE-1 and -2). The main goal of our study was to analyze the possible redundant and specific roles of the two PCPE proteins during wound healing.Interestingly, both BTPs and PCPE-1 were found to be expressed in the dermis and to be significantly increased during the first week after injury. Surprisingly, PCPE-1 is mainly expressed by dermal fibroblasts, whereas PCPE-2 is lowly expressed in fibroblasts and more abundant in basal keratinocytes. Moreover, PCPE-2 appears to be expressed by myeloid cells suggesting that PCPE-2 might rather play a role during the inflammatory phase of wound healing. In addition, our results indicate that recombinant PCPE 2 does not efficiently enhance their proteolytic maturation of fibrillar procollagens and can even inhibit the action of BMP-1 on other non-collagenous substrates, suggesting a differential and unexpected role of PCPE-2. Finally, the in vivo role of PCPE-2 was investigated using a Pcolce2 knockout model; skin morphology and wound healing were not affected by PCPE-2 loss, indicating that PCPE-1 is the main enhancer involved in collagen deposition during wound healing. Thus, this work suggests that PCPE-1 and -2 play distinct roles in the skin and during wound healing
 
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Moali, Catherine

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