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

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

Research output: Contribution to journalArticle

77 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

ASJC Scopus subject areas

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

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