文章基本信息

标题：Pannexin 1 involvement in bladder dysfunction in a multiple sclerosis model
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作者：Hiromitsu Negoro ; Sarah E. Lutz ; Louis S. Liou 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2013
卷号：3
期号：1
DOI：10.1038/srep02152
语种：English
出版社：Springer Nature
摘要：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.