Intracellular transport in the progress of chronic liver disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08287
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Osaka University
• Principal Investigator: Sakamori Ryotaro 大阪大学, 大学院医学系研究科, 特任講師 (10644685)
• Co-Investigator(Kenkyū-buntansha): 巽 智秀 大阪大学, 大学院医学系研究科, 准教授 (20397699) ; 疋田 隼人 大阪大学, 大学院医学系研究科, 講師 (20623044)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 脂肪生成

Outline of Final Research Achievements

Differentiation of mesenchymal stem cells into adipocytes requires external stimuli, and it is not known how the transport network regulated by Rab8, a Small GTPase, affects mesenchymal tissue differentiation. In this study, we show that Rab8-deficient mouse embryonic fibroblasts (MEFs) are inhibited in their differentiation into adipocytes; examination of MEFs lacking Rab8a and Rab8b revealed that Rab8 attenuates Wnt signaling in differentiating MEFs and inhibits lipid droplet formation in Rab8a-/- and/or Rab8b KD MEFs, suggesting that Rab8 is involved in the differentiation of cilia. formation and abnormal cilia morphology were observed in Rab8a-/- and Rab8b KD MEFs. These results suggest that intracellular trafficking regulates the induction of adipogenesis via Wnt receptors in mesenchymal cells.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

非アルコール性脂肪性肝疾患（NAFLD）／非アルコール性脂肪肝炎（NASH）は、慢性肝疾患の原因の一つであり、NASH は肝硬変や肝細胞癌に進展しうる。我が国におけるNAFLD の有病率は9～30％、NASH においては3～5％と推定され、ともに増加傾向と推測されている。NAFLD/NASHは内臓脂肪と関連し、脂肪細胞の発生についての理解が脂肪肝に対する加療において不可欠である。我々は細胞内輸送の観点から、脂肪細胞の分化誘導について検討を行った。本研究成果は脂肪肝成立メカニズムを理解する上で意義があると考えられる。