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

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-?B (NF-?B) 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-?B activation and intracellular H2O2 accumulation. In primary keratinocyte cultures, cellular import of H2O2 produced by membrane NADPH oxidase 2 (Nox2) in response to TNF-? is facilitated by AQP3 and required for NF-?B 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-? stimulation. Collectively, these data indicate that AQP3-facilitated H2O2 transport is required for NF-?B activation in keratinocytes in the development of psoriasis.

SUBMITTER: Hara-Chikuma M

PROVIDER: S-EPMC5628617 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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

Hara-Chikuma Mariko M Satooka Hiroki H Watanabe Sachiko S Honda Tetsuya T Miyachi Yoshiki Y Watanabe Takeshi T Verkman A S AS

Nature communications 20150623

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 me ...[more]

PMID: 26100668

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Project description:Aquaporin-8 (AQP8), a member of the aquaporin family, is strongly expressed in follicular granulosa cells, which could affect the hormone secretion level in females. AQP8, as a membrane protein, could mediate H2O2 into cells, thereby triggering various biological events. The deficiency of Aqp8 increases female fertility, resulting from the decrease in follicular atresia. The low cell death rate is related to the apoptosis of granulosa cells. However, the mechanism by which AQP8 regulates the autophagy of granulosa cells remains unclear. Thus, this study aimed to explore the effect of AQP8 on autophagy in follicular atresia. We found that the expression of the autophagy marker light-chain protein 3 was significantly downregulated in the granulosa cells of Aqp8-knockout (Aqp8 -/- ) mice, compared with wild-type (Aqp8 +/+ ) mice. Immunofluorescence staining and transmission electron microscopic examination indicated that the number of autophagosomes in the granulosa cells of Aqp8 -/- mice decreased. Using a follicular granulosa cell autophagy model, namely a follicular atresia model, we verified that the concentration of H2O2 significantly increased during the autophagy of granulosa cells, consistent with the Aqp8 mRNA level. Intracellular H2O2 accumulation was modulated by endogenous AQP8 expression level, indicating that AQP8-mediated H2O2 was involved in the autophagy of granulosa cells. AQP8 deficiency impaired the elevation of H2O2 concentration through phosphorylated tyrosine activation. In addition, we carried out the analysis of transcriptome sequencing datasets in the ovary and found there were obvious differences in principal components, differentially expressed genes (DEGs) and KEGG pathways, which might be involved in AQP8-regulated follicular atresia. Taken together, these findings indicated that AQP8-mediated H2O2 transport could mediate the autophagy of granulosa cells. AQP8 might be a potential target for diseases related to ovarian insufficiency.

Dataset Information

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

Publications

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

Similar Datasets

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