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Title: LPA induces keratinocyte differentiation and promotes skin barrier function through the LPAR1/LPAR5-RHO-ROCK-SRF axis
Authors: Sumitomo, Akiko
Siriwach, Ratklao
Thumkeo, Dean
Ito, Kentaro
Nakagawa, Ryota
Tanaka, Nobuo  kyouindb  KAKEN_id
Tanabe, Kohei
Watanabe, Akira
Kishibe, Mari
Ishida-Yamamoto, Akemi
Honda, Tetsuya
Kabashima, Kenji
Aoki, Junken
Narumiya, Shuh
Author's alias: 住友, 明子
タムケオ, ディーン
田中, 信生
田邊, 滉平
渡辺, 亮
岸部, 麻里
山本, 明美
本田, 哲也
椛島, 健治
青木, 淳賢
成宮, 周
Issue Date: May-2019
Publisher: Elsevier BV
Journal title: Journal of Investigative Dermatology
Volume: 139
Issue: 5
Start page: 1010
End page: 1022
Abstract: The skin barrier protects our body from water loss, allergens and pathogens. Profilaggrin (proFLG) is produced by differentiated keratinocytes and is processed into FLG monomers. These monomers crosslink keratin filaments and are also decomposed to natural moisturizing factors in the stratum corneum for skin hydration and barrier function. Deficits in FLG expression impair skin barrier function and underlie skin diseases such as dry skin and atopic dermatitis (AD). However, intrinsic factors that regulate FLG expression and their mechanism of action remain unknown. Here, we show that lysophosphatidic acid (LPA) induces FLG expression in human keratinocytes via the LPAR1 and LPAR5 receptors and the downstream RHO-ROCK-SRF pathway. Comprehensive gene profiling analysis further revealed that LPA not only induces FLG expression but also facilitates keratinocyte differentiation. Moreover, LPA treatment significantly upregulated FLG production in a three-dimensional culture model of human skin, and promoted barrier function in mouse skin in vivo. Thus, our work demonstrates a previously unsuspected role for LPA and its downstream signaling in the maintenance of skin homeostasis, which may serve as a novel therapeutic target for skin barrier dysfunction.
Description: ヒト表皮細胞の分化と皮膚バリア機能の調節機構を解明 --アトピー性皮膚炎の新たな治療戦略へ向けて--. 京都大学プレスリリース. 2018-11-16.
Rights: © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
The full-text file will be made open to the public on 1 May 2020 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1016/j.jid.2018.10.034
PubMed ID: 30447238
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