An Aquaporin 3-Notch1 Axis in Keratinocyte Differentiation and Inflammation

OPEN ACCESS PEER-REVIEWED

RESEARCH ARTICLE

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  Liqiong Guo,
 
• Hongxiang Chen,
 
• Yongsheng Li,
 
• Qixing Zhou mail,
 
• Yang Sui mail

Abstract

Aquaporin 3 (AQP3) is an aquaglyceroporin which transports water, glycerol and small solutes across the plasma membrane. Its functions are not limited to fluid transport but also involve the regulation of cell proliferation, migration, skin hydration, wound healing and tumorigenesis. While AQP3 has been reported to play an important role in keratinocyte proliferation, its role in differentiation remains controversial. Our study demonstrated that the expression of AQP3 was regulated during differentiation and that it participated in keratinocyte differentiation control. We further revealed that AQP3 was a transcriptional target of Notch signaling, a critical pathway regulating keratinocyte differentiation and tumor suppression, and it regulated differentiation through a reciprocal negative feedback loop with Notch1. When the expression level of AQP3 was elevated, impaired barrier integrity and increased pro-inflammatory cytokine production ensued, mimicking the pathological conditions in Notch deficient mice and in atopic dermatitis. Dysregulation of AQP3 and Notch receptors has been reported in several skin diseases, including skin cancer. Our discovery of the novel AQP3-Notch1 axis may provide insight into epidermal homeostasis control and possible translational applications, including its potential use as a biomarker for molecular diagnosis in environmental studies.
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Citation: Guo L, Chen H, Li Y, Zhou Q, Sui Y (2013) An Aquaporin 3-Notch1 Axis in Keratinocyte Differentiation and Inflammation. PLoS ONE 8(11): e80179. doi:10.1371/journal.pone.0080179
Editor: Andrzej T Slominski, University of Tennessee, United States of America
Received: August 6, 2013; Accepted: October 4, 2013; Published: November 8, 2013
Copyright: © 2013 Guo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by grants from China Ministry of Science and Technology (2011CB503802 to QXZ), National Natural Science Foundation of China as a key project (grant No. 21037002 to QXZ) and National Natural Science Foundation of China Grants (grant No. 81171495 and 81271765 to HXC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
• Published: Nov 08, 2013
• DOI: 10.1371/journal.pone.0080179
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