from the poplar mecano-perception to visceral sensitivity in mice: role of ubiquitous transcription...
TRANSCRIPT
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
Réunion annuelle du Groupe Français de Neuro-Gastroenterologie
20-21 juin 2013
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 syndromeIBD : intestinal bowel desease
Colonic hypersensitivity
Colonic pain
2/3 of cases
INTRODUCTION
Colonic hypersensitivity
Colonic pain
2/3 of cases
Exarcerbated response to painful stimulation or not
INTRODUCTION
Peripheral sensitization (target organ)
Peripheral sensor
Mechanical sensor
INTRODUCTION
Inflammation mediator
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
Martin, 2009
INTRODUCTION
Martin, 2009
INTRODUCTION
Martin, 2010
Martin, 2009
Mechanosensor in plant genetic equivalent in animal
PtaZFP2 EGR-4
INTRODUCTION
Martin, 2010
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.
Involvement in visceral
mechanosensation?
Expression of EGR-4 in colon?
OBJECTIFS
Target genes?
Sensibilization?
Involvement in visceral
mechanosensation?
Expression of EGR-4 in colon?
OBJECTIFS
Target genes?
Sensibilization?
distension
Euthanasia
1h30 2h0 45 min30 min15 min10 min5 min 1h
PROTOCOLE
Western Blot
Increase of total form of EGR-4 45 minutes after distension
Expression of EGR-4
EGR-4 Colon
Increase of total form of EGR-4 45 minutes after distension
Expression of EGR-4
EGR-4 Colon
Increase of total form of EGR-4 120 minutes after distension
Expression of EGR-4
EGR-4 DRGv
Increase of total form of EGR-4 90 minutes after distension
Expression of EGR-4
EGR-4 DRGv
Expression of EGR-4
Increase of total form of EGR-4 45 minutes after distension
EGR-4 Spinal Cord
Expression of EGR-4
Increase of total form of EGR-4 45 minutes after distension
EGR-4 Spinal Cord
Conclusion & percpectives
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
Conclusion & perspectives
Conclusion
News tools
expression in colon, DRG and spinal cord.
Modulation expression with mechanical stimulation
Acknowledgement
Thank you for your attention
Monique Etienne
Ludivine Boudieu
Emilie Muller
Agathe Gelot
Frederic Carvalho
Denis Ardid