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Alison Accarie / 2 ème année de thèse Directeur de thèse : Pr. Michel Dapoigny

Réunion annuelle du Groupe Français de Neuro-Gastroenterologie 20-21 juin 2013. 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

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Alison Accarie / 2 ème année de thèse Directeur de thèse : Pr. Michel Dapoigny

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  1. Réunion annuelle du Groupe Français de Neuro-Gastroenterologie 20-21 juin 2013 From the Poplar mecano-perception to visceral sensitivity in mice: role of ubiquitous transcription factor EGR-4? Alison Accarie / 2ème 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

  2. 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

  3. INTRODUCTION Colonic pain 2/3 of cases Colonic hypersensitivity

  4. INTRODUCTION Colonic pain 2/3 of cases Colonic hypersensitivity • Exarcerbated response to painful stimulation or not • Peripheral sensitization (target organ)

  5. INTRODUCTION Peripheral sensor Mechanical sensor Inflammation mediator

  6. INTRODUCTION Identification of a new transcription factor in case of mechanical stimulation in Arabidopsis & Poplar sp. (Equipe MECA, UMR PIAF Clermont-Ferrand) PTaZFP2 Transcription factor Zinc finger Early expression

  7. INTRODUCTION Martin, 2009

  8. INTRODUCTION Martin, 2009 Martin, 2010

  9. INTRODUCTION Martin, 2009 Martin, 2010 Mechanosensor in plant genetic equivalent in animal PtaZFP2 EGR-4

  10. INTRODUCTION EGR Family: 4 subtypes (EGR-1) Transcription factor/ EarlyGene Response Zinc fingers structure/ Same DNA bindingsequence : GCC G/TGG GCG EGR-4 • Male unfertility • Inflammatory process in cultured T cell Surexpression in somatosensory cortex after mechanical stimulation.

  11. OBJECTIFS Expression of EGR-4 in colon? Involvement in visceral mechanosensation? Target genes? Sensibilization?

  12. OBJECTIFS Expression of EGR-4 in colon? Involvement in visceral mechanosensation? Target genes? Sensibilization?

  13. PROTOCOLE Euthanasia distension 10 min 15 min 30 min 45 min 1h 1h30 2h 5 min 0  Western Blot

  14. EGR-4 Colon Expression of EGR-4 Increase of total form of EGR-4 45 minutes after distension

  15. EGR-4 Colon Expression of EGR-4 Increase of total form of EGR-4 45 minutes after distension

  16. EGR-4 DRGv Expression of EGR-4 Increase of total form of EGR-4 120 minutes after distension

  17. EGR-4 DRGv Expression of EGR-4 Increase of total form of EGR-4 90 minutes after distension

  18. EGR-4 Spinal Cord Expression of EGR-4 Increase of total form of EGR-4 45 minutes after distension

  19. EGR-4 Spinal Cord Expression of EGR-4 Increase of total form of EGR-4 45 minutes after distension

  20. Conclusion & percpectives • Conclusion • News tools • expression in colon, DRG and spinal cord. • Modulation expression with mechanical stimulation

  21. Conclusion & perspectives • Conclusion • News tools • expression in colon, DRG and spinal cord. • Modulation expression with mechanical stimulation Future studies • mRNA expression studies (qPCR) • Identification of target genes (micro-array) • Different models of colonic Hypersensitivity

  22. Acknowledgement Monique Etienne Ludivine Boudieu Emilie Muller Agathe Gelot Frederic Carvalho Denis Ardid Thank you for your attention

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