Regulation of epithelial cell charactor by phosphoinositide
| Project/Area Number |
17H04051
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
Fukami Kiyoko 東京薬科大学, 生命科学部, 教授 (40181242)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | イノシトールリン脂質 / 表皮バリア機能 / 細胞膜外葉 / 細胞接着 / 上皮細胞 / 表皮細胞 / がん細胞 / リン脂質代謝 / 上皮細胞の特性 / リン脂質 / 皮膚疾患 |
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| Outline of Final Research Achievements |
First, we showed that downregulation of phospholipase C (PLC)d1 impairs the barrier functions of the SC. PLCd1 downregulation also impairs localization of tight junction proteins. Loss of PLCd1 leads to a decrease in intracellular Ca2+ concentrations and NFAT activity, along with hyperactivation of MAPK and inactivation of RhoA. These findings demonstrate that PLCd1 is essential for epidermal barrier integrity.
Next we found that phosphatidylinositol 4,5-bisphosphate (PIP2) was detected in the cell surface of non-permeabilized cells by anti-PIP2 antibodies and the PIP2 probe. Cell surface PIP2 signal was universally detected in various cell lines. Furthermore, blocking cell surface PIP2 by the addition of anti-PIP2 antibody or the PIP2 probe inhibited cell attachment, spreading, and migration. These results indicate a unique localization of PIP2 in the outer leaflet that may have a crucial role in cell attachment, spreading, and migration.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は、リン脂質代謝酵素PLCδ1の不全が、NFATの不活性化、p38MAPKの異常活性化、RhoAの不活性化を介して表皮顆粒層のタイトジャンクション不良を誘導し、表皮細胞バリア機能の破綻を誘導することを明らかにした。こうした表皮細胞バリア機能の異常は乾癬などの炎症性皮膚炎で観察されることから、新たな治療法として発展する可能性がある。
また、イノシトールリン脂質PIP2が細胞膜外葉にも存在すること、細胞膜外葉PIP2が細胞接着や細胞運動に関与することを明らかにした。こうした事実はこれまで考えられてきたリン脂質の役割の概念を変えるものであり、細胞生物学の進展に大きく寄与することが期待できる。
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Report
(4 results)
Research Products
(39 results)
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[Journal Article] PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis.2017
Author(s)
Hirabayashi T, Anjo T, Kaneko A, Senoo Y, Shibata A, Takama H, Yokoyama K, Nishito Y, Ono T, Taya C, Muramatsu K, Fukami K, Muñoz-Garcia A, Brash A, Ikeda K, Arita M, Akiyama M, Murakami M.
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Journal Title
Nat. Commun.
Volume: 8
Pages: 14609-14609
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Phospholipase Cδ1 regulates p38 MAPK activity and skin barrier integrity.2017
Author(s)
Kaori Kanemaru, Yoshikazu Nakamura, Kengo Totoki, Takatsugu Fukuyama, Madoka Shoji, Hisae Kaneko, Kanako Shiratori, Atsuko Yoneda, Takafumi Inoue, Yoichiro Iwakura, Kenji Kabashima, Kiyoko Fukami
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Journal Title
Cell Death Differ.
Volume: in press
Pages: 1079-1090
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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