Primary cilia-mediated signaling for cell growth and differentiation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02696
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Mie University
• Principal Investigator: Inagaki Masaki 三重大学, 医学系研究科, 客員教授 (30183007)
• Co-Investigator(Kenkyū-buntansha): 西村 有平 三重大学, 医学系研究科, 教授 (30303720) ; 山川 大史 三重大学, 医学系研究科, 助教 (20631097)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 一次線毛 / 脂肪前駆細胞 / 細胞分化 / 細胞増殖 / 脂質ラフト / カベオラ

Outline of Final Research Achievements

We have found that trichoplein (TCHP), a ciliogenesis inhibitor identified by us, affects primary cilia elongation in pre-adipocytes in TCHP KO mice, and this suppresses insulin-Akt signaling. TCHP KO mice have anti-obesity effect, and we analyzed various adipose differentiation markers in visceral fat. We revealed that white adipose tissue becomes beige adipose tissue increasing thermogenic ability. Furthermore, ectopic fat accumulation in the liver was suppressed, and we are currently analyzing this. We also generated KCTD17-deficient mice, which have an antagonistic effect on TCHP, and analyzed whether there is an opposite effect on primary cilia formation or an obesity-promoting effect, and the molecular mechanism of primary cilia formation and adipocyte differentiation was clarified.

Free Research Field

病態生理学

Academic Significance and Societal Importance of the Research Achievements

脂肪前駆細胞において、一次線毛を伸長させるメカニズムの詳細を明確にすることで、細胞の分化をコントロールできるようになり、脂肪細胞量や脂肪量を調節することができるようになる。内臓脂肪や皮下脂肪では、直接脂肪前駆細胞の一次線毛が伸長して、細胞分化を制御していることが考えられるが、肝臓などの異所性脂肪蓄積には間接的な関与が考えられ、本研究の遂行は一次線毛を標的とした新たな治療法の創出に貢献できることが期待できる。