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

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 - 2013

Fingerprint

Interleukin-1
Multiple Sclerosis
Connexin 43
Autoimmune Experimental Encephalomyelitis
Urinary Bladder
Urination
p38 Mitogen-Activated Protein Kinases
Cellular Mechanotransduction
Up-Regulation
Phosphorylation
Mefloquine
Mucous Membrane
Coloring Agents
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

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

Pannexin 1 involvement in bladder dysfunction in a multiple sclerosis model. / Negoro, Hiromitsu; Lutz, Sarah E.; Liou, Louis S.; Kanematsu, Akihiro; Ogawa, Osamu; Scemes, Eliana; Suadicani, Sylvia O.

In: Scientific Reports, Vol. 3, 2152, 2013.

Research output: Contribution to journalArticle

Negoro H, Lutz SE, Liou LS, Kanematsu A, Ogawa O, Scemes E et al. Pannexin 1 involvement in bladder dysfunction in a multiple sclerosis model. Scientific Reports. 2013;3. 2152. https://doi.org/10.1038/srep02152
Negoro, Hiromitsu ; Lutz, Sarah E. ; Liou, Louis S. ; Kanematsu, Akihiro ; Ogawa, Osamu ; Scemes, Eliana ; Suadicani, Sylvia O. / Pannexin 1 involvement in bladder dysfunction in a multiple sclerosis model. In: Scientific Reports. 2013 ; Vol. 3.
@article{858aafba92bd4d6da3aca2ac9c2bd4c9,
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.",
author = "Hiromitsu Negoro and Lutz, {Sarah E.} and Liou, {Louis S.} and Akihiro Kanematsu and Osamu Ogawa and Eliana Scemes and Suadicani, {Sylvia O.}",
year = "2013",
doi = "10.1038/srep02152",
language = "English (US)",
volume = "3",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Pannexin 1 involvement in bladder dysfunction in a multiple sclerosis model

AU - Negoro, Hiromitsu

AU - Lutz, Sarah E.

AU - Liou, Louis S.

AU - Kanematsu, Akihiro

AU - Ogawa, Osamu

AU - Scemes, Eliana

AU - Suadicani, Sylvia O.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84881366962&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881366962&partnerID=8YFLogxK

U2 - 10.1038/srep02152

DO - 10.1038/srep02152

M3 - Article

C2 - 23827947

AN - SCOPUS:84881366962

VL - 3

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 2152

ER -