Upregulation of Aquaporin-3 Is Involved in Keratinocyte Proliferation and Epidermal Hyperplasia
Upregulation of Aquaporin-3 Is Involved in Keratinocyte Proliferation and Epidermal Hyperplasia
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DOI：
10.1038/jid.2010.395
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发表时间：
2011-04-01
影响因子：
6.5
通讯作者：
Hara-Chikuma, Mariko
中科院分区：
文献类型：
--
作者：
Nakahigashi, Kyoko;Kabashima, Kenji;Hara-Chikuma, Mariko
Aquaporin-3 (AQP3) 是一种在表皮角质形成细胞中表达的水/甘油转运蛋白。我们之前表明，AQP3 介导的水和甘油转运分别参与角质形成细胞迁移和增殖。然而，AQP3 与特应性皮炎 (AD) 等皮肤病表皮增生的关系尚不清楚。在这项研究中，我们发现人类 AD 病变表皮中 AQP3 转录物和蛋白表达显着增加。通过人 AQP3 DNA 质粒转染，人角质形成细胞中 AQP3 表达上调与细胞甘油和 ATP 增加以及细胞增殖增加相关。在皮肤产生的多种细胞因子和趋化因子中，CCL17 在 AD 中高表达，被发现是 AQP3 表达和增强角质形成细胞增殖的强诱导剂。在小鼠 AD 模型中，AQP3 在野生型小鼠的表皮中强烈过度表达。 AQP3 缺陷小鼠的表皮增生减少，角质形成细胞数量减少。这些结果表明，AQP3 通过上调 AQP3 表达并随后增强角质形成细胞增殖的机制参与表皮增生。皮肤病学研究杂志 (2011) 131, 865-873； doi：10.1038/jid.2010.395； 2010 年 12 月 30 日在线发布
Aquaporin-3 (AQP3) is a water/glycerol-transporting protein expressed in keratinocytes of the epidermis. We previously showed that AQP3-mediated transport of water and glycerol is involved in keratinocyte migration and proliferation, respectively. However, the involvement of AQP3 in epidermal hyperplasia in skin diseases, such as atopic dermatitis (AD), is unknown. In this study, we found significantly increased AQP3 transcript and protein expression in the epidermis of human AD lesions. The upregulation of AQP3 expression in human keratinocytes by transfection with human AQP3 DNA plasmid was associated with increased cellular glycerol and ATP, as well as increased cell proliferation. Among several cytokines and chemokines produced in the skin, CCL17, which is highly expressed in AD, was found to be a strong inducer of AQP3 expression and enhanced keratinocyte proliferation. In mouse AD models, AQP3 was strongly overexpressed in the epidermis in wild-type mice. Epidermal hyperplasia was reduced in AQP3-deficient mice, with a decreased number of proliferating keratinocytes. These results suggest the involvement of AQP3 in epidermal hyperplasia by a mechanism involving upregulated AQP3 expression and consequent enhancement of keratinocyte proliferation. Journal of Investigative Dermatology (2011) 131, 865-873; doi:10.1038/jid.2010.395; published online 30 December 2010