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

Mariko Hara-Chikuma (), Hiroki Satooka, Sachiko Watanabe, Tetsuya Honda, Yoshiki Miyachi, Takeshi Watanabe and A. S. Verkman
Additional contact information
Mariko Hara-Chikuma: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University
Hiroki Satooka: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University
Sachiko Watanabe: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University
Tetsuya Honda: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University
Yoshiki Miyachi: Graduate School of Medicine, Kyoto University
Takeshi Watanabe: Center for Innovation in Immunoregulative Technology and Therapeutics, Graduate School of Medicine, Kyoto University
A. S. Verkman: University of California

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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 factor-κB (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.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms8454 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8454

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms8454

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().