TY - JOUR
T1 - Aquaporin-3-mediated hydrogen peroxide transport is required for NF-ΰ B signalling in keratinocytes and development of psoriasis
AU - Hara-Chikuma, Mariko
AU - Satooka, Hiroki
AU - Watanabe, Sachiko
AU - Honda, Tetsuya
AU - Miyachi, Yoshiki
AU - Watanabe, Takeshi
AU - Verkman, A. S.
N1 - Funding Information:
We thank Atsuko Shibayama for mouse breeding, Drs Shu Narumiya and Shunsuke Chikuma for helpful discussions. This work was supported by grants from Astellas Pharma Inc. in the Creation of Innovation Centers for Advanced Inter disciplinary Research Areas Program, and the Ministry of Education, Culture, Sports, Science and Technology of Japan (M.H.-C.), and grant DK35124 from the U.S. National Institutes of Health (A.S.V.).
Publisher Copyright:
© 2015 Macmillan Publishers Limited.
PY - 2015/6/23
Y1 - 2015/6/23
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms8454
DO - 10.1038/ncomms8454
M3 - Article
C2 - 26100668
AN - SCOPUS:84934904648
SN - 2041-1723
VL - 6
JO - Nature communications
JF - Nature communications
M1 - 7454
ER -