title: Colonic overexpression of the T-type calcium channel Cav3.2 in a mouse model of visceral hypersensitivity and in irritable bowel syndrome patients.
abstract: BACKGROUND
  Among the different mechanisms involved in irritable bowel syndrome (IBS) physiopathology, visceral hypersensitivity seems to play a key role. It involves sensitization of the colonic primary afferent fibers, especially through an overexpression of ion channels. The aims of this translational study were to investigate the colonic expression of Cav3.2 calcium channels and their involvement in an animal model of colonic hypersensitivity, and to assess their expression in the colonic mucosa of symptomatic IBS patients.
  
  
  METHODS
  This bench-to-bed study combined a preclinical experimental study on mice and a case-control clinical study. Preclinical studies were performed on wild-type and Cav3.2-KO mice. Colonic sensitivity and Cav3.2 expression were studied after a low-dose treatment of dextran sodium sulfate (DSS 0.5%). Regarding the clinical study, colonic biopsies were performed in 14 IBS patients and 16 controls during a colonoscopy to analyze the mucosal Cav3.2 expression.
  
  
  RESULTS
  Wild-type, but not Cav3.2-KO, mice developed visceral hypersensitivity without colonic inflammation, after 0.5% DSS treatment. A significant increase of Cav3.2 mRNA (p = 0.04) was found in the colon of low-dose DSS-treated wild-type (WT) mice compared to their controls. In human colonic biopsies, the Cav3.2 mRNA level was significantly higher in the IBS group compared to the control group (p = 0.01). The immunofluorescence staining revealed their protein expression in colonic mucosa, particularly in nerve fibers.
  
  
  CONCLUSIONS
  This translational study supports the involvement of the calcium channels Cav3.2 in abdominal pain, as observed in IBS patients. It opens new therapeutic perspectives based on molecules specifically blocking these channels.
authors.affiliation: Centre Hospitalier Universitaire Estaing, Department of Digestive Diseases, CHU Clermont-Ferrand, Clermont-Ferrand, France. jscanzi@chu-clermontferrand.fr.|Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France. jscanzi@chu-clermontferrand.fr.
authors.forename: J
authors.initials: J
authors.lastname: Scanzi
authors.affiliation: Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France.
authors.forename: A
authors.initials: A
authors.lastname: Accarie
authors.affiliation: Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France.
authors.forename: E
authors.initials: E
authors.lastname: Muller
authors.affiliation: Centre Hospitalier Universitaire G. Montpied, Biostatistics Unit (DRCI), CHU Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: B
authors.initials: B
authors.lastname: Pereira
authors.affiliation: Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Aissouni
authors.affiliation: Centre Hospitalier Universitaire Estaing, Department of Digestive Diseases, CHU Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: M
authors.initials: M
authors.lastname: Goutte
authors.affiliation: Centre Hospitalier Universitaire Estaing, Department of Histopathology, CHU Estaing Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: J
authors.initials: J
authors.lastname: Joubert-Zakeyh
authors.affiliation: Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France.
authors.forename: E
authors.initials: E
authors.lastname: Picard
authors.affiliation: Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France.
authors.forename: L
authors.initials: L
authors.lastname: Boudieu
authors.affiliation: Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France.
authors.forename: C
authors.initials: C
authors.lastname: Mallet
authors.affiliation: Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France.
authors.forename: A
authors.initials: A
authors.lastname: Gelot
authors.affiliation: Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France.
authors.forename: D
authors.initials: D
authors.lastname: Ardid
authors.affiliation: Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France.
authors.forename: F A
authors.initials: FA
authors.lastname: Carvalho
authors.affiliation: Centre Hospitalier Universitaire Estaing, Department of Digestive Diseases, CHU Clermont-Ferrand, Clermont-Ferrand, France.|Inserm UMR 1107 Neurodol/Université d'Auvergne, Medicine Faculty of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France.
authors.forename: M
authors.initials: M
authors.lastname: Dapoigny
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000096:biosynthesis* / Q000235:genetics; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D059265:Visceral Pain / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C479952:CACNA1H protein, human; D020747:Calcium Channels, T-Type
keywords: calcium channel; colonic hypersensitivity; irritable bowel syndrome; visceral pain