title: Pannexin 1 involvement in bladder dysfunction in a multiple sclerosis model.
abstract: Bladder dysfunction is common in Multiple Sclerosis (MS) but little is known of its pathophysiology. We show that mice with experimental autoimmune encephalomyelitis (EAE), a MS model, have micturition dysfunction and altered expression of genes associated with bladder mechanosensory, transduction and signaling systems including pannexin 1 (Panx1) and Gja1 (encoding connexin43, referred to here as Cx43). EAE mice with Panx1 depletion (Panx1(-/-)) displayed similar neurological deficits but lesser micturition dysfunction compared to Panx1(+/+) EAE. Cx43 and IL-1β upregulation in Panx1(+/+) EAE bladder mucosa was not observed in Panx1(-/-) EAE. In urothelial cells, IL-1β stimulation increased Cx43 expression, dye-coupling, and p38 MAPK phosphorylation but not ERK1/2 phosphorylation. SB203580 (p38 MAPK inhibitor) prevented IL-1β-induced Cx43 upregulation. IL-1β also increased IL-1β, IL-1R-1, PANX1 and CASP1 expression. Mefloquine (Panx1 blocker) reduced these IL-1β responses. We propose that Panx1 signaling provides a positive feedback loop for inflammatory responses involved in bladder dysfunction in MS.
authors.affiliation: Department of Urology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Negoro
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lutz
authors.forename: Louis S
authors.initials: LS
authors.lastname: Liou
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kanematsu
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
authors.forename: Eliana
authors.initials: E
authors.lastname: Scemes
authors.forename: Sylvia O
authors.initials: SO
authors.lastname: Suadicani
mesh_terms: D000818:Animals; D018031:Connexin 43 / Q000235:genetics; D017630:Connexins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000235:genetics; D051379:Mice; D009103:Multiple Sclerosis / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D001743:Urinary Bladder / Q000503:physiopathology*
chemical_list: D018031:Connexin 43; D017630:Connexins; D053583:Interleukin-1beta; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; D011494:Protein Kinases