Mechanism of liquid-air phase-dependent differentiation in cultured keratinocyte

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19228
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Agricultural chemistry and related fields
• Research Institution: Nagoya University
• Principal Investigator: Hitomi Kiyotaka 名古屋大学, 創薬科学研究科, 教授 (00202276)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: 表皮形成 / 羊水 / 空気暴露 / タンパク質架橋化酵素

Outline of Final Research Achievements

In my research human keratinocyte differentiation have been studied using three-dimensional culture system, where air exposure is essential for keratinization with multilayer. In order to clarify the mechanism by which air-exposure causes differentiation, search for mRNAs and proteins which might cause cellular signaling on the initiation of differentiation. By comparison with mRNAs from day 2-cultrue (air and liquid), several candidates of specific key molecules were identified and their characterization is ongoing.
In paralleled with this approach, the amniotic fluid from mouse uterus were investigated for their component by mass spectrometric analysis and its ability to promote differentiation. Skin formation during several fetal days were analyzed for barrier function as well as transglutaminase activity. Partial purification is underway based on the promoting activity for keratinocyte differentiation using several marker proteins.

Free Research Field

応用生物化学

Academic Significance and Societal Importance of the Research Achievements

立体培養系における、ヒト表皮細胞の分化促進の刺激メカニズムとしての空気暴露は極めてユニークで前例のないものであり、その後のシグナル伝達解明は全く新奇な系を見出す可能性がある。これは表皮分化の新たな機構を確立しうるほか、新たな分化促進因子を見出す手掛かりにもなりうる。
一方で、マウスの羊水中に表皮細胞分化を促進する物質を検出できたので、今後は精製を進めて同定する。これはヒトの表皮再生に有用な因子となりうる他、母体の生育環境評価を羊水で行う際にも有用な評価基準として用いられるため、研究、医療、畜産の広い分野に波及効果をもたらす可能性がある。