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From the Poplar mecano-perception to visceral sensitivity in mice: role of ubiquitous transcription factor EGR-4? Alison Accarie / 2 ème année de thèse Directeur de thèse : Pr. Michel Dapoigny Directeurs du laboratoire : Pr. Alain Eschalier et Pr. Denis Ardid UMR/INSERM 1107 Neuro Dol, Pharmacologie Fondamentale et Clinique de la douleur Réunion annuelle du Groupe Français de Neuro-Gastroenterologie 20-21 juin 2013
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INTRODUCTION U1107 / Pharmacologie fondamentale et clinique de la douleur inadequate support of chronic pain Visceral pain Abdominal pain Colonic pain First cause for gastroenterological consultation Common symptoms of IBS et IBD (period of remission) IBS : irritable bowel syndrome IBD : intestinal bowel desease
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Colonic hypersensitivity Colonic pain 2/3 of cases INTRODUCTION
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Colonic hypersensitivity Colonic pain 2/3 of cases Exarcerbated response to painful stimulation or not INTRODUCTION Peripheral sensitization (target organ)
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Peripheral sensor Mechanical sensor INTRODUCTION Inflammation mediator
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Identification of a new transcription factor in case of mechanical stimulation in Arabidopsis & Poplar sp. (Equipe MECA, UMR PIAF Clermont-Ferrand) INTRODUCTION PTaZFP2 Transcription factor Zinc finger Early expression
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Martin, 2009 INTRODUCTION
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Martin, 2009 INTRODUCTION Martin, 2010
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Martin, 2009 Mechanosensor in plant genetic equivalent in animal PtaZFP2EGR-4 INTRODUCTION Martin, 2010
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EGR Family: 4 subtypes (EGR-1) Transcription factor/ Early Gene Response Zinc fingers structure/ Same DNA binding sequence : GCC G/TGG GCG INTRODUCTION EGR-4 Male unfertility Inflammatory process in cultured T cell Surexpression in somatosensory cortex after mechanical stimulation.
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Involvement in visceral mechanosensation? Expression of EGR-4 in colon? OBJECTIFS Target genes? Sensibilization?
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Involvement in visceral mechanosensation? Expression of EGR-4 in colon? OBJECTIFS Target genes? Sensibilization?
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distension Euthanasia 1h302h 0 45 min30 min15 min10 min 5 min 1h PROTOCOLE Western Blot
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Increase of total form of EGR-4 45 minutes after distension Expression of EGR-4 EGR-4 Colon
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Increase of total form of EGR-4 45 minutes after distension Expression of EGR-4 EGR-4 Colon
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Increase of total form of EGR-4 120 minutes after distension Expression of EGR-4 EGR-4 DRGv
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Increase of total form of EGR-4 90 minutes after distension Expression of EGR-4 EGR-4 DRGv
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Expression of EGR-4 Increase of total form of EGR-4 45 minutes after distension EGR-4 Spinal Cord
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Expression of EGR-4 Increase of total form of EGR-4 45 minutes after distension EGR-4 Spinal Cord
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Conclusion & percpectives Conclusion News tools expression in colon, DRG and spinal cord. Modulation expression with mechanical stimulation
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Future studies mRNA expression studies (qPCR) Identification of target genes (micro-array) Different models of colonic Hypersensitivity Conclusion & perspectives Conclusion News tools expression in colon, DRG and spinal cord. Modulation expression with mechanical stimulation
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Acknowledgement Thank you for your attention Monique Etienne Ludivine Boudieu Emilie Muller Agathe Gelot Frederic Carvalho Denis Ardid
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