| First Author | Negoro H | Year | 2013 |
| Journal | Sci Rep | Volume | 3 |
| Pages | 2152 | PubMed ID | 23827947 |
| Mgi Jnum | J:232001 | Mgi Id | MGI:5775709 |
| Doi | 10.1038/srep02152 | Citation | Negoro H, et al. (2013) Pannexin 1 involvement in bladder dysfunction in a multiple sclerosis model. Sci Rep 3:2152 |
| abstractText | 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-1beta upregulation in Panx1(+/+) EAE bladder mucosa was not observed in Panx1(-/-) EAE. In urothelial cells, IL-1beta stimulation increased Cx43 expression, dye-coupling, and p38 MAPK phosphorylation but not ERK1/2 phosphorylation. SB203580 (p38 MAPK inhibitor) prevented IL-1beta-induced Cx43 upregulation. IL-1beta also increased IL-1beta, IL-1R-1, PANX1 and CASP1 expression. Mefloquine (Panx1 blocker) reduced these IL-1beta responses. We propose that Panx1 signaling provides a positive feedback loop for inflammatory responses involved in bladder dysfunction in MS. |
