Regulation of primary cilia formation by the ubiquitinーproteasome system

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03448
• 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: Kasahara Kousuke 三重大学, 医学系研究科, 准教授 (90455535)
• Co-Investigator(Kenkyū-buntansha): 白水 崇 三重大学, 医学系研究科, 助教 (00582678) ; 山川 大史 三重大学, 医学系研究科, 助教 (20631097)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 一次線毛 / 肥満 / 骨格筋再生 / シグナル伝達

Outline of Final Research Achievements

Primary cilia play pivotal roles in signal transduction and development, and are known to serve as signaling hubs. In this study, we show that genetic ablation of trichoplein (Tchp) induces ciliary elongation on adipose progenitors (APs) in skin and fibro-adipogenic progenitors (FAPs) in injured skeletal muscle. The elongated cilia on APs suppress adipogenic differentiation by disrupting cilia-dependent lipid raft dynamics, which protects mice from high fat diet-induced obesity. Furthermore, the elongated cilia on FAPs accelerate interleukin 13 secretion from FAPs, which promotes skeletal muscle regeneration. further of APs and promote regeneration of muscle fibers. Overall, our results suggest a novel role for primary cilia in regulating adipogenesis and skeletal muscle regeneration.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、一次線毛が肥満や骨格筋再生に関与していることをマウス実験で証明し、その分子機序の一端についても明らかにした。本研究を発展させることで、肥満やその関連疾患や、老化による筋力低下、筋ジストロフィなどの難治性筋疾患の分子機序の解明や、治療法や診断法の開発につながることが期待できる。また、本研究で作製したトリコプレインノックアウトマウスは、肥満及びその関連疾患に抵抗性を持つ画期的なマウスモデルとして利用できる。