Aquaporin-3-mediated hydrogen peroxide transport is required for NF-ΰ B signalling in keratinocytes and development of psoriasis

Mariko Chikuma, Hiroki Satooka, Sachiko Watanabe, Tetsuya Honda, Yoshiki Miyachi, Takeshi Watanabe, A. S. Verkman

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Aquaporin 3 (AQP3), a water/glycerol channel protein, has been found to transport hydrogen peroxide (H2O2). Here, we show that H2O2, imported via AQP3, is involved in nuclear factorkB (NF-κB) signalling in keratinocytes and in the pathogenesis of psoriasis. IL-23-mediated induction of psoriasis is reduced in AQP3 knockout mice (AQP3-/-), and is accompanied by impaired NF-κB activation and intracellular H2O2 accumulation. In primary keratinocyte cultures, cellular import of H2O2 produced by membrane NADPH oxidase 2 (Nox2) in response to TNF-α is facilitated by AQP3 and required for NF-κB activation by regulation of protein phosphatase 2A. As AQP3 associates with Nox2, we propose that this interplay constitutes H2O2-mediated signalling in response to TNF-α stimulation. Collectively, these data indicate that AQP3-facilitated H2O2 transport is required for NF-κB activation in keratinocytes in the development of psoriasis.

Original languageEnglish
Article number7454
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 2015 Jun 23
Externally publishedYes

Fingerprint

Aquaporin 3
hydrogen peroxide
Keratinocytes
Psoriasis
Hydrogen Peroxide
oxidase
activation
knockout mice
proteins
pathogenesis
phosphatases
glycerols
stimulation
NADPH Oxidase
Chemical activation
induction
membranes
Interleukin-23
Protein Phosphatase 2
Aquaporins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)
  • Medicine(all)

Cite this

Aquaporin-3-mediated hydrogen peroxide transport is required for NF-ΰ B signalling in keratinocytes and development of psoriasis. / Chikuma, Mariko; Satooka, Hiroki; Watanabe, Sachiko; Honda, Tetsuya; Miyachi, Yoshiki; Watanabe, Takeshi; Verkman, A. S.

In: Nature Communications, Vol. 6, 7454, 23.06.2015.

Research output: Contribution to journalArticle

Chikuma, Mariko ; Satooka, Hiroki ; Watanabe, Sachiko ; Honda, Tetsuya ; Miyachi, Yoshiki ; Watanabe, Takeshi ; Verkman, A. S. / Aquaporin-3-mediated hydrogen peroxide transport is required for NF-ΰ B signalling in keratinocytes and development of psoriasis. In: Nature Communications. 2015 ; Vol. 6.
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