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.
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
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 7454
ER -