| First Author | Hara-Chikuma M | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7454 | PubMed ID | 26100668 |
| Mgi Jnum | J:223017 | Mgi Id | MGI:5646334 |
| Doi | 10.1038/ncomms8454 | Citation | Hara-Chikuma M, et al. (2015) Aquaporin-3-mediated hydrogen peroxide transport is required for NF-kappaB signalling in keratinocytes and development of psoriasis. Nat Commun 6:7454 |
| abstractText | 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-kappaB (NF-kappaB) 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-kappaB activation and intracellular H2O2 accumulation. In primary keratinocyte cultures, cellular import of H2O2 produced by membrane NADPH oxidase 2 (Nox2) in response to TNF-alpha is facilitated by AQP3 and required for NF-kappaB 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-alpha stimulation. Collectively, these data indicate that AQP3-facilitated H2O2 transport is required for NF-kappaB activation in keratinocytes in the development of psoriasis. |
