Research Team

Translational approach to epithelial injury and repair

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HomeTeamsTranslational approach to epithelial injury and repair

Our team is interested in the membrane receptor called RAGE (advanced glycation end products receptor) which is a multi-ligand receptor (called alarmins) belonging to the immunoglobulin superfamily. The binding of one of its ligands will trigger at the cellular level signalling cascades leading to the arinsing of an inflammatory response. Our project is particularly interested in the involvement of this receptor in the lung and fetal membranes (water pocket) focusing on epithelial cells and their aggression as a result of 2 pathologies: acute respiratory distress syndrome and premature rupture of fetal membranes.

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Following aggressions resulting from both exogenous and endogenous signals, the achievement of the integrity and functioning of the epithelial barrier is an essential element found in many human pathological situations. The abilities to repair such epithelial aggression condition the pejorative or favorable evolution of these clinical events. Located at the crossroads of many metabolic and/or inflammatory processes, the receptor for advanced glycation end-products (RAGE) appears to be a promising signaling pathway to be investigated in the context of this epithelial dysfunction. The team has begun to demonstrate this on two models of amniotic and pulmonary epithelial aggression present in the wake of two common and serious pathologies, respectively premature rupture of fetal membranes (PROM) and acute respiratory distress syndrome (ARDS). In view of the complexity of the possible combinations «ligands/ RAGE isoforms» associated with the pathological activation of the RAGE pathway, it appears essential to identify the relative importance of these different combinations and to determine whether new ligands cannot be specifically involved in PROM and/or ARDS. Using pharmacological and molecular approaches developed in parallel on our two models of epithelial aggression, this project also aims to identify abnormally modulated molecular pathways and target genes during the activation of the RAGE pathway that may be associated with the cascading of pathophysiological events encountered during these two pathologies. As the interaction of the epithelium with the cells of its immediate environment is a strong determinant of the evolution of aggression, our work also aims to demonstrate the impact of the RAGE pathway in cellular communications. Finally, the availability of KO mice for RAGE will allow to study in vivo, the impacts of a modulation of this route. Our results should make it possible to obtain diagnostic, prognostic and therapeutic advances focused on the RABIES signaling pathway during epithelial aggressions.



74 publications

CX3CL1/Fractalkine as a biomarker for early pregnancy prediction of preterm premature rupture of membranes.

Published on 26 Jan 2024 in Clinical chemistry and laboratory medicine

Kahouadji S , Giguère Y, Lambert S, Forest JC, Bernard N, Blanchon L , Marceau G , Durif J, Pereira B, Gallot D , Sapin V , Bouvier D

Nanoscale silicate melt textures determine volcanic ash surface chemistry.

Published on 15 Jan 2024 in Nature communications , vol. 15 - pp 531

Hornby AJ, Ayris PM, Damby DE, Diplas S, Eychenne J , Kendrick JE, Cimarelli C, Kueppers U, Scheu B, Utley JEP, Dingwell DB

Prevalence of FGF23 elevation in patients with hypophosphatemia.

Published on 13 Jan 2024 in Clinica chimica acta; international journal of clinical chemistry , vol. 554 - pp 117782

Oris C , Lautrette A, Dougé A, Bouraima F, Kahouadji S , Pickering ME, Garrouste C, Gagnière J, Guièze R, D'Ostrevy N, Futier E , Grobost V, Buisson A, Batisse M, Bouillon-Minois JB, Pereira B, Durif J, Sapin V , Bouvier D


Effectiveness and Costs of Molecular Screening and Treatment for Bacterial Vaginosis to Prevent Preterm Birth: The AuTop Randomized Clinical Trial.

Published on 01 Sep 2023 in JAMA pediatrics , vol. 177 - pp 894-902

Bretelle F, Loubière S, Desbriere R, Loundou A, Blanc J, Heckenroth H, Schmitz T, Benachi A, Haddad B, Mauviel F, Danoy X, Mares P, Chenni N, Ménard JP, Cocallemen JF, Slim N, Sénat MV, Chauleur C, Bohec C, Kayem G, Trastour C , Bongain A, Rozenberg P, Serazin V, Fenollar F, Groupe de Recherche en Obstetrique et Gynécologie (GROG) Investigators

Characterization of RAGE and CK2 Expressions in Human Fetal Membranes.

Published on 17 Feb 2023 in International journal of molecular sciences , vol. 24

Coste K , Bruet S , Chollat-Namy C , Filhol O, Cochet C, Gallot D , Marceau G , Blanchon L , Sapin V , Belville C


Risk Factors and Outcomes of Preterm Premature Rupture of Membranes in a Cohort of 6968 Pregnant Women Prospectively Recruited.

Published on 15 Nov 2019 in Journal of clinical medicine , vol. 8

Bouvier D , Forest JC, Blanchon L , Bujold E, Pereira B, Bernard N, Gallot D , Sapin V , Giguère Y

Retinoic Acid Pathway Regulation of Vascular Endothelial Growth Factor in Ovine Amnion.

Published on 30 Oct 2019 in Reproductive sciences (Thousand Oaks, Calif.) , vol. 26 - pp 1351-1359

Cheung CY, Anderson DF, Rouzaire M , Blanchon L , Sapin V , Brace RA

Driving pressure and acute respiratory distress syndrome in critically ill patients.

Published on 02 Mar 2019 in Respirology (Carlton, Vic.) , vol. 24 - pp 137-145

Blondonnet R , Joubert E, Godet T, Berthelin P, Pranal T, Roszyk L , Chabanne R, Eisenmann N, Lautrette A, Belville C , Cayot S, Gillart T, Souweine B, Bouvier D , Blanchon L , Sapin V , Pereira B, Constantin JM , Jabaudon M


Serum soluble receptor for advanced glycation end-products during acute bronchiolitis in infant: Prospective study in 93 cases.

Published on 30 Oct 2018 in Pediatric pulmonology , vol. 53 - pp 1429-1435

Egron C, Roszyk L , Rochette E, Jabaudon M , Sapin V , Mulliez A, Labbé A, Coste K

Clinical validation of S100B in the management of a mild traumatic brain injury: issues from an interventional cohort of 1449 adult patients.

Published on 25 Oct 2018 in Clinical chemistry and laboratory medicine , vol. 56 - pp 1897-1904

Allouchery G, Moustafa F, Roubin J, Pereira B, Schmidt J, Raconnat J, Pic D, Sapin V , Bouvier D

Plasma sRAGE is independently associated with increased mortality in ARDS: a meta-analysis of individual patient data.

Published on 30 Sep 2018 in Intensive care medicine , vol. 44 - pp 1388-1399

Jabaudon M , Blondonnet R , Pereira B, Cartin-Ceba R, Lichtenstern C, Mauri T, Determann RM, Drabek T, Hubmayr RD, Gajic O, Uhle F, Coppadoro A, Pesenti A, Schultz MJ, Ranieri MV, Brodska H, Mrozek S, Sapin V , Matthay MA, Constantin JM , Calfee CS

The Biomarker S100B and Mild Traumatic Brain Injury: A Meta-analysis.

Published on 30 Jun 2018 in Pediatrics , vol. 141

Oris C , Pereira B, Durif J, Simon-Pimmel J, Castellani C, Manzano S, Sapin V , Bouvier D

Recent directions in personalised acute respiratory distress syndrome medicine.

Published on 30 Jun 2018 in Anaesthesia, critical care & pain medicine , vol. 37 - pp 251-258

Jabaudon M , Blondonnet R , Audard J, Fournet M , Godet T, Sapin V , Constantin JM

Clinical and Biological Predictors of Plasma Levels of Soluble RAGE in Critically Ill Patients: Secondary Analysis of a Prospective Multicenter Observational Study.

Published on 10 May 2018 in Disease markers , vol. 2018 - pp 7849675

Pranal T, Pereira B, Berthelin P, Roszyk L , Godet T, Chabanne R, Eisenmann N, Lautrette A, Belville C , Blondonnet R , Cayot S, Gillart T, Skrzypczak Y, Souweine B, Bouvier D , Blanchon L , Sapin V , Constantin JM , Jabaudon M

Receptor for advanced glycation end-products and ARDS prediction: a multicentre observational study.

Published on 08 Feb 2018 in Scientific reports , vol. 8 - pp 2603

Jabaudon M , Berthelin P, Pranal T, Roszyk L , Godet T, Faure JS, Chabanne R, Eisenmann N, Lautrette A, Belville C , Blondonnet R , Cayot S, Gillart T, Pascal J, Skrzypczak Y, Souweine B, Blanchon L , Sapin V , Pereira B, Constantin JM

Vitamin A status in healthy women eating traditionally prepared spirulina (Dihé) in the Chad Lake area.

Published on 29 Jan 2018 in PloS one , vol. 13 - pp e0191887

Soudy ID, Minet-Quinard R , Mahamat AD, Ngoua HF, Izzedine AA, Tidjani A, Ngo Bum E, Lambert C, Pereira B, Desjeux JF, Sapin V

High frequency percussive ventilation increases alveolar recruitment in early acute respiratory distress syndrome: an experimental, physiological and CT scan study.

Published on 11 Jan 2018 in Critical care (London, England) , vol. 22 - pp 3

Godet T, Jabaudon M , Blondonnet R , Tremblay A, Audard J, Rieu B, Pereira B, Garcier JM, Futier E , Constantin JM


Recruitment maneuvers in acute respiratory distress syndrome.

Published on 30 Jul 2017 in Annals of translational medicine , vol. 5 - pp 290

Constantin JM , Godet T, Jabaudon M , Bazin JE, Futier E

Retinoic Acid Engineered Amniotic Membrane Used as Graft or Homogenate: Positive Effects on Corneal Alkali Burns.

Published on 01 Jul 2017 in Investigative ophthalmology & visual science , vol. 58 - pp 3513-3518

Joubert R, Daniel E, Bonnin N, Comptour A , Gross C , Belville C , Chiambaretta F , Blanchon L , Sapin V

[Premature rupture of membranes≥37 weeks of gestation: Predictive factors for labour onset within 24hours].

Published on 30 Jun 2017 in Gynecologie, obstetrique, fertilite & senologie , vol. 45 - pp 348-352

Huret C, Pereira B, Collange V, Delabaere A , Rouzaire M , Lemery D, Sapin V , Gallot D

Epidural analgesia in critically ill patients with acute pancreatitis: the multicentre randomised controlled EPIPAN study protocol.

Published on 29 May 2017 in BMJ open , vol. 7 - pp e015280

Bulyez S, Pereira B, Caumon E, Imhoff E, Roszyk L , Bernard L, Bühler L, Heidegger C, Jaber S, Lefrant JY, Chabanne R, Bertrand PM, Laterre PF, Guerci P, Danin PE, Escudier E, Sossou A, Morand D, Sapin V , Constantin JM , Jabaudon M , EPIPAN Study Group, AzuRea network

Utility of S100B Serum Level for the Determination of Concussion in Male Rugby Players.

Published on 30 Apr 2017 in Sports medicine (Auckland, N.Z.) , vol. 47 - pp 781-789

Bouvier D , Duret T, Abbot M, Stiernon T, Pereira B, Coste A, Chazal J, Sapin V

Sevoflurane for Sedation in Acute Respiratory Distress Syndrome. A Randomized Controlled Pilot Study.

Published on 15 Mar 2017 in American journal of respiratory and critical care medicine , vol. 195 - pp 792-800

Jabaudon M , Boucher P, Imhoff E, Chabanne R, Faure JS, Roszyk L , Thibault S, Blondonnet R , Clairefond G , Guérin R, Perbet S , Cayot S, Godet T, Pereira B, Sapin V , Bazin JE, Futier E , Constantin JM


Elevated Plasma Levels of sRAGE Are Associated With Nonfocal CT-Based Lung Imaging in Patients With ARDS: A Prospective Multicenter Study.

Published on 30 Nov 2016 in Chest , vol. 150 - pp 998-1007

Mrozek S, Jabaudon M , Jaber S, Paugam-Burtz C, Lefrant JY, Rouby JJ, Asehnoune K, Allaouchiche B, Baldesi O, Leone M, Lu Q, Bazin JE, Roszyk L , Sapin V , Futier E , Pereira B, Constantin JM , Azurea network

Lung ultrasonography for assessment of oxygenation response to prone position ventilation in ARDS.

Published on 30 Oct 2016 in Intensive care medicine , vol. 42 - pp 1546-1556

Haddam M, Zieleskiewicz L, Perbet S , Baldovini A, Guervilly C, Arbelot C, Noel A, Vigne C, Hammad E, Antonini F, Lehingue S, Peytel E, Lu Q, Bouhemad B, Golmard JL, Langeron O, Martin C, Muller L, Rouby JJ, Constantin JM , Papazian L, Leone M, CAR’Echo Collaborative Network, AzuRea Collaborative Network

Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons.

Published on 30 Sep 2016 in International journal of radiation biology , vol. 92 - pp 527-35

Dionet C, Müller-Barthélémy M, Marceau G , Denis JM, Averbeck D, Gueulette J, Sapin V , Pereira B, Tchirkov A, Chautard E, Verrelle P

Lysyl oxidase-like 4 involvement in retinoic acid epithelial wound healing.

Published on 06 Sep 2016 in Scientific reports , vol. 6 - pp 32688

Comptour A , Rouzaire M , Belville C , Bonnin N, Daniel E, Chiambaretta F , Blanchon L , Sapin V

Effect of non-invasive oxygenation strategies in immunocompromised patients with severe acute respiratory failure: a post-hoc analysis of a randomised trial.

Published on 30 Aug 2016 in The Lancet. Respiratory medicine , vol. 4 - pp 646-652

Frat JP, Ragot S, Girault C, Perbet S , Prat G, Boulain T, Demoule A, Ricard JD, Coudroy R, Robert R, Mercat A, Brochard L, Thille AW, REVA network

Preanalytical, analytical, gestational and pediatric aspects of the S100B immuno-assays.

Published on 30 May 2016 in Clinical chemistry and laboratory medicine , vol. 54 - pp 833-42

Bouvier D , Duret T, Rouzaire P, Jabaudon M , Rouzaire M , Nourrisson C, Bourgne C, Pereira B, Evrard B, Sapin V

Net alveolar fluid clearance is associated with lung morphology phenotypes in acute respiratory distress syndrome.

Published on 30 Apr 2016 in Anaesthesia, critical care & pain medicine , vol. 35 - pp 81-6

Jabaudon M , Blondonnet R , Lutz J, Roszyk L , Bouvier D , Guérin R, Perbet S , Cayot S, Godet T, Blanchon L , Bazin JE, Futier E , Sapin V , Constantin JM

Effect of Noninvasive Ventilation on Tracheal Reintubation Among Patients With Hypoxemic Respiratory Failure Following Abdominal Surgery: A Randomized Clinical Trial.

Published on 05 Apr 2016 in JAMA , vol. 315 - pp 1345-53

Jaber S, Lescot T, Futier E , Paugam-Burtz C, Seguin P, Ferrandiere M, Lasocki S, Mimoz O, Hengy B, Sannini A, Pottecher J, Abback PS, Riu B, Belafia F, Constantin JM , Masseret E, Beaussier M, Verzilli D, De Jong A, Chanques G, Brochard L, Molinari N, NIVAS Study Group


Aquaporins and Fetal Membranes From Diabetic Parturient Women: Expression Abnormalities and Regulation by Insulin.

Published on 30 Oct 2015 in The Journal of clinical endocrinology and metabolism , vol. 100 - pp E1270-9

Bouvier D , Rouzaire M , Marceau G , Prat C , Pereira B, Lemarié R, Deruelle P, Fajardy I, Gallot D , Blanchon L , Vambergue A, Sapin V

Comment and reply on: Guidelines for the management of spontaneous preterm labor: identification of spontaneous preterm labor, diagnosis of preterm premature rupture of membranes, and preventive tools for preterm birth.

Published on 17 Jun 2015 in The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians - pp 1-2

Gallot D , Goffinet F, Sapin V , Guibourdenche J, Jouannic M, Langer B, Doret M, Subtil D, Fernandez H

High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure.

Published on 04 Jun 2015 in The New England journal of medicine , vol. 372 - pp 2185-96

Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S , Prat G, Boulain T, Morawiec E, Cottereau A, Devaquet J, Nseir S, Razazi K, Mira JP, Argaud L, Chakarian JC, Ricard JD, Wittebole X, Chevalier S, Herbland A, Fartoukh M, Constantin JM , Tonnelier JM, Pierrot M, Mathonnet A, Béduneau G, Delétage-Métreau C, Richard JC, Brochard L, Robert R, FLORALI Study Group, REVA Network

IFPA meeting 2014 workshop report: Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetics and epigenetics; the placenta and stillbirth and fetal growth restriction.

Published on 30 Apr 2015 in Placenta , vol. 36 Suppl 1 - pp S5-10

Barbaux S, Erwich JJ, Favaron PO, Gil S, Gallot D , Golos TG, Gonzalez-Bulnes A, Guibourdenche J, Heazell AE, Jansson T, Laprévote O, Lewis RM, Miller RK, Monk D, Novakovic B, Oudejans C, Parast M, Peugnet P, Pfarrer C, Pinar H, Roberts CT, Robinson W, Saffery R, Salomon C, Sexton A, Staff AC, Suter M, Tarrade A, Wallace J, Vaillancourt C, Vaiman D, Worton SA, Lash GE

Metabolic disturbances of the vitamin A pathway in human diaphragmatic hernia.

Published on 15 Jan 2015 in American journal of physiology. Lung cellular and molecular physiology , vol. 308 - pp L147-57

Coste K , Beurskens LW, Blanc P , Gallot D , Delabaere A , Blanchon L , Tibboel D, Labbé A, Rottier RJ, Sapin V


An interplay of geometry and signaling enables robust lung branching morphogenesis.

Published on 30 Dec 2014 in Development (Cambridge, England) , vol. 141 - pp 4526-36

Menshykau D, Blanc P , Unal E, Sapin V , Iber D

The challenge of prenatal identification of congenital diaphragmatic hernia in the context of hydrops.

Published on 30 Nov 2014 in European journal of obstetrics, gynecology, and reproductive biology , vol. 182 - pp 238-9

Rossi A, Delabaere A , Delmas-Laurichesse H, Beaufrère AM, Lémery D, Gallot D

Endocrine gland-derived endothelial growth factor (EG-VEGF) is a potential novel regulator of human parturition.

Published on 30 Sep 2014 in Biology of reproduction , vol. 91 - pp 73

Dunand C, Hoffmann P, Sapin V , Blanchon L , Salomon A, Sergent F, Benharouga M, Sabra S, Guibourdenche J, Lye SJ, Feige JJ, Alfaidy N

Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a.

Published on 07 Aug 2014 in Cell reports , vol. 8 - pp 743-53

Deplus R, Blanchon L , Rajavelu A, Boukaba A, Defrance M, Luciani J, Rothé F, Dedeurwaerder S, Denis H, Brinkman AB, Simmer F, Müller F, Bertin B , Berdasco M, Putmans P, Calonne E, Litchfield DW, de Launoit Y, Jurkowski TP, Stunnenberg HG, Bock C, Sotiriou C, Fraga MF, Esteller M, Jeltsch A, Fuks F

Atherogenic subfractions of lipoproteins in the treatment of metabolic syndrome by physical activity and diet – the RESOLVE trial.

Published on 11 Jul 2014 in Lipids in health and disease , vol. 13 - pp 112

Dutheil F, Walther G, Chapier R, Mnatzaganian G, Lesourd B, Naughton G, Verney J, Fogli A , Sapin V , Duclos M, Vinet A, Obert P, Courteix D, Lac G

Lung postmortem autopsy revealing extramedullary involvement in multiple myeloma causing acute respiratory distress syndrome.

Published on 01 Jan 2014 in Case reports in hematology , vol. 2014 - pp 635237

Ravinet A, Perbet S , Guièze R, Lemal R, Guérin R, Gayraud G, Aliane J, Tremblay A, Pascal J, Ledoux A, Chaleteix C, Dechelotte P , Bay JO, Bazin JE, Constantin JM


Plasma levels of sRAGE, loss of aeration and weaning failure in ICU patients: a prospective observational multicenter study.

Published on 27 May 2013 in PloS one , vol. 8 - pp e64083

Jabaudon M , Perbet S , Pereira B, Soummer A, Roszyk L , Guérin R, Futier E , Lu Q, Bazin JE, Sapin V , Rouby JJ, Constantin JM


Fetal skin fibroblasts: a cell model for studying the retinoid pathway in congenital diaphragmatic hernia.

Published on 30 Mar 2010 in Birth defects research. Part A, Clinical and molecular teratology , vol. 88 - pp 195-200

Goumy C, Coste K , Marceau G , Gouas L, Tchirkov A, Vago P, Gallot D , Sapin V

Retinoid pathway and congenital diaphragmatic hernia: hypothesis from the analysis of chromosomal abnormalities.

Published on 01 Jan 2010 in Fetal diagnosis and therapy , vol. 28 - pp 129-39

Goumy C, Gouas L, Marceau G , Coste K , Veronese L, Gallot D , Sapin V , Vago P, Tchirkov A


Natural mutations of the anti-Mullerian hormone type II receptor found in persistent Mullerian duct syndrome affect ligand binding, signal transduction and cellular transport.

Published on 15 Aug 2009 in Human molecular genetics , vol. 18 - pp 3002-13

Belville C , Maréchal JD, Pennetier S, Carmillo P, Masgrau L, Messika-Zeitoun L, Galey J, Machado G, Treton D, Gonzalès J, Picard JY, Josso N, Cate RL, di Clemente N


11 theses
Effects of sevoflurane in the treatment of Acute respiratory Distress Syndrome : a translational approach
Realized by :
Ruoyang Zhai
Defense date:
Dérégulation de l’expression du Récepteur aux Produits Avancés de Glycation (RAGE) dans la pathologie de la Surface oculaire
Realized by :
Valentin NAVEL
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Inflammation du syndrome de l’oeil sec : implications épithéliales et macrophagiques de NFAT5 et RAGE
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Effects of sevoflurane on RAGE-mediated pathways of lung injury and repair : a translational approach
Realized by :
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Implications du récepteur aux produits avancés de glycation, RAGE, dans la physiopathologie de la rupture des membranes fœtales humaines
Realized by :
Helena Choltus
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Role des protéines NLRP dans la physopathologie des membranes foetales humaines
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Etude de l’implication des produits de glycation avancés et de leur récepteur RAGE dans la cicatrisation de l’épithélium cornéen
Realized by :
Christelle GROSS
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Rétinoïdes en intra-tracheal et occlusion de trachée dans le traitement anténatal de la hernie diaphragmatique congénitale
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Fonctions des rétinoïdes dans les membranes fœtales humaines : action pro-cicatrisante médiée par LOXL4
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L’ATRA (Acide tout trans rétinoïque), dérivé actif de la vitamine A permet la cicatrisation de cellules épithéliales de cornée humaine HCE et de l’épithélium cornéen brulé par base chez le modèle souris
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Ontogénèse et régulation des aquaporines par les rétinoïdes dans ls membranes fœtales humaines
Realized by :
Cécile PRAT
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