Pannexin 1 involvement in bladder dysfunction in a multiple sclerosis model

Hiromitsu Negoro, Sarah E. Lutz, Louis S. Liou, Akihiro Kanematsu, Osamu Ogawa, Eliana Scemes, Sylvia O. Suadicani

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28 Scopus citations

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.

Original languageEnglish (US)
Article number2152
JournalScientific Reports
Volume3
DOIs
StatePublished - Aug 15 2013

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    Negoro, H., Lutz, S. E., Liou, L. S., Kanematsu, A., Ogawa, O., Scemes, E., & Suadicani, S. O. (2013). Pannexin 1 involvement in bladder dysfunction in a multiple sclerosis model. Scientific Reports, 3, [2152]. https://doi.org/10.1038/srep02152