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Biochem Biophys Res Commun. 2009 Sep 25;387(3):564-8. doi: 10.1016/j.bbrc.2009.07.077. Epub 2009 Jul 18.

Tumor necrosis factor-alpha decreases aquaporin-3 expression in DJM-1 keratinocytes.

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  • 1Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, Japan.


Aquaporin-3 (AQP3) is a water/glycerol-transporting protein that is strongly expressed at the plasma membranes of keratinocytes in skin. There is evidence for involvement of AQP3-facilitated water and glycerol transport in skin hydration and wound repair, respectively. In this study, we show that tumor necrosis factor-alpha (TNF-alpha) and TNF receptor-1 signaling decreased AQP3 protein expression and plasma membrane water permeability in DJM-1 keratinocytes. TNF-alpha also decreased AQP3 mRNA expression and promoter activity, indicating that TNF-alpha suppresses AQP3 gene transcription. In addition, inhibitors of p38 and extracellular signal-regulated kinase (ERK) abolished the effect of TNF-alpha on AQP3 expression level, whereas inhibitors for NF-kappaB did not. These data indicate that TNF-alpha decreases AQP3 gene expression through p38 and ERK activation, and suggest that the decrease in AQP3 expression caused by TNF-alpha might be related to the phenotypes of skin inflammation, such as dry skin.

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