Upregulation of aquaporin-3 is involved in keratinocyte proliferation and epidermal hyperplasia

Kyoko Nakahigashi, Kenji Kabashima, Akihiko Ikoma, Alan S. Verkman, Yoshiki Miyachi, Mariko Chikuma

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)865-873
Number of pages9
JournalJournal of Investigative Dermatology
Volume131
Issue number4
DOIs
Publication statusPublished - 2011 Apr
Externally publishedYes

Fingerprint

Aquaporin 3
Keratinocytes
Hyperplasia
Up-Regulation
Atopic Dermatitis
Epidermis
Glycerol
Skin
Water
Cell proliferation
Chemokines
Skin Diseases
Transfection

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Upregulation of aquaporin-3 is involved in keratinocyte proliferation and epidermal hyperplasia. / Nakahigashi, Kyoko; Kabashima, Kenji; Ikoma, Akihiko; Verkman, Alan S.; Miyachi, Yoshiki; Chikuma, Mariko.

In: Journal of Investigative Dermatology, Vol. 131, No. 4, 04.2011, p. 865-873.

Research output: Contribution to journalArticle

Nakahigashi, Kyoko ; Kabashima, Kenji ; Ikoma, Akihiko ; Verkman, Alan S. ; Miyachi, Yoshiki ; Chikuma, Mariko. / Upregulation of aquaporin-3 is involved in keratinocyte proliferation and epidermal hyperplasia. In: Journal of Investigative Dermatology. 2011 ; Vol. 131, No. 4. pp. 865-873.
@article{6ce18e6ebc50492689ffaad8284f54d3,
title = "Upregulation of aquaporin-3 is involved in keratinocyte proliferation and epidermal hyperplasia",
abstract = "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.",
author = "Kyoko Nakahigashi and Kenji Kabashima and Akihiko Ikoma and Verkman, {Alan S.} and Yoshiki Miyachi and Mariko Chikuma",
year = "2011",
month = "4",
doi = "10.1038/jid.2010.395",
language = "English",
volume = "131",
pages = "865--873",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Upregulation of aquaporin-3 is involved in keratinocyte proliferation and epidermal hyperplasia

AU - Nakahigashi, Kyoko

AU - Kabashima, Kenji

AU - Ikoma, Akihiko

AU - Verkman, Alan S.

AU - Miyachi, Yoshiki

AU - Chikuma, Mariko

PY - 2011/4

Y1 - 2011/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79952769780&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952769780&partnerID=8YFLogxK

U2 - 10.1038/jid.2010.395

DO - 10.1038/jid.2010.395

M3 - Article

C2 - 21191421

AN - SCOPUS:79952769780

VL - 131

SP - 865

EP - 873

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 4

ER -