| Project/Area Number |
24591643
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | University of Toyama |
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Principal Investigator |
MAKINO Teruhiko 富山大学, 大学院医学薬学研究部(医学), 准教授 (90359711)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Tadamichi 富山大学, 大学院医学薬学研究部(医学), 教授 (70260396)
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| Co-Investigator(Renkei-kenkyūsha) |
HIBINO Toshihiko 資生堂リサーチセンター, セニアサイエンティスト
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | プロフィラグリン / 皮膚 / 表皮角化細胞 / 細胞死 / アポトーシス / profilaggrin / 終末分化 / 角化 / 皮膚がん / 皮膚癌 |
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| Outline of Final Research Achievements |
Profilaggrin plays a critical role in keratinocyte terminal differentiation. During this process, a 55-kDa N-terminal fragment of profilaggrin (proFLG-N) is translocated into the nucleus. In this study, we examined a function of FLG-N in keratinocytes and elucidated the molecular mechanisms of the terminal differentiation.
Interestingly, proFLG-N was liberated by epidermal mesotrypsin and was translocated into the nucleus; thereafter, the cells became TUNEL positive. This finding was also observed when A-domain of proFLG-N, but not proB-domain, was translocated into the nucleus. Furthermore, caspase-14 caused limited proteolysis of ICAD, followed by accumulation of CAD in TUNEL-positive nuclei. Knockdown of both proteases resulted in a significant increase of remnant nuclei in a skin equivalent model. Collectively, our results indicate that at least two pathways are involved in the DNA degradation process during keratinocyte terminal differentiation.
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