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Involvement of Rho effector molecules on the homeostasis of stratum corneum barrier

Research Project

Project/Area Number 17K10214
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionOita University

Principal Investigator

Hatano Yutaka  大分大学, 医学部, 教授 (80336263)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
KeywordsRho / ROCK / mDia / skin barrier / mDia / 皮膚バリア / 皮膚炎 / 皮膚バリア機能 / 生体分子 / 皮膚生理
Outline of Final Research Achievements

(1) Spontaneous dermatitis occurred in keratinocyte-specific ROCK1/2 deficient mice. Histopathologically, epidermal thickening, inflammatory cell infiltration, and an increase in mast cells in the dermis were observed. Elevated levels of IgE, TSLP and IL-6 in serum were also detected. Immunohistochemical staining revealed abnormal distribution or reduction of expression of differentiation-related proteins.
(2) In keratinocyte-specific mDia1/3 deficient mice (K5Cre-mDia1/3KO mice), substance permeability test revealed that the skin permeability barrier was reduced. Levels of mRNA expression of enzymes involved in lipid metabolism, which are important in the formation of the intercellular lipid membrane of the stratum corneum, is not clearly different from those of wild-type mice. Electron microscopic analysis suggested decreased secretion of lamellar bodies in K5Cre-mDia1/3KO mice. Meanwhile, the amount of ceramide in the stratum corneum in K5Cre-mDia1/3KO mice tended to increase.

Academic Significance and Societal Importance of the Research Achievements

本研究は、Rhoからのシグナルは、透過性バリア機能のみでなく、表皮角化細胞における炎症関連機能にも深く関与していることを示唆している。今後、炎症性皮膚疾患における、表皮角化細胞のRhoとその下流蛋白の役割が明瞭になれば、表皮恒常性の破綻の炎症性皮膚疾患の病態における意義が明確になると期待される。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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