Project/Area Number |
24248055
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Clinical veterinary science
|
Research Institution | Tokyo University of Agriculture and Technology |
Principal Investigator |
MATSUDA Hiroshi 東京農工大学, (連合)農学研究科(研究院), 教授 (80145820)
|
Co-Investigator(Kenkyū-buntansha) |
TANAKA Akane 東京農工大学, 大学院農学研究院, 教授 (80418673)
OHMORI Keitaro 東京農工大学, 大学院農学研究院, 講師 (20466915)
MATSUDA Akira 東京農工大学, 大学院農学研究院, 助教 (90613969)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥32,370,000 (Direct Cost: ¥24,900,000、Indirect Cost: ¥7,470,000)
Fiscal Year 2014: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2013: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2012: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
|
Keywords | トランスレーショナルリサーチ / 動物 / 酵素 / ストレス |
Outline of Final Research Achievements |
Raised skin pH may result in enzymatic activation of kallikrein 5 (KLK5), a serine protease thought to play a crucial role in skin barrier destruction. Although skin surface pH is increased in patients with atopic dermatitis (AD), contribution of pH to initiation of AD has been unclear. By using NC/Tnd mice, a model for human AD, skin pH and transepidermal water loss (TEWL), as well as KLK5, protease-activated receptor 2 (PAR2), and thymic stromal lymphopoietin (TSLP) were measured. Acidification of the skin reduced KLK5 activity in the epidermis and ameliorated the eczema. In contrast, alkalization of the skin increased epidermal expression of KLK5 and TEWL, resulting in development of AD, even in SPF NC/Tnd mice without AD. Skin surface pH modulates KLK5 production, which might directly be responsible for barrier dysfunction, itch sensation, and allergic inflammation by activating a PAR2 and TSLP cascade in the epidermis.
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