Analysis of molecular mechanism in keratinocyte terminal differentiation

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591643
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: University of Toyama
• Principal Investigator: MAKINO Teruhiko 富山大学, 大学院医学薬学研究部(医学), 准教授 (90359711)
• 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)
• 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
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: プロフィラグリン / 皮膚 / 表皮角化細胞 / 細胞死

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.

Free Research Field

皮膚科学