Molecular mechanism of regulation of cellular functions by extracellular matrix stiffness

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02167
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 38060:Applied molecular and cellular biology-related
• Research Institution: Kyoto University
• Principal Investigator: Kioka Noriyuki 京都大学, 農学研究科, 教授 (90234179)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 細胞外マトリックス / コラーゲン / 細胞接着 / 間葉系幹細胞 / 接着斑

Outline of Final Research Achievements

The stiffness of extracellular matrix such as collagen regulates the cell differentiation. In this study, we investigated the involvement of the vinculin-SORBS3/1 axis. We found that both SORBS3 and SORBS1 regulate the nuclear localization of YAP in a manner dependent on the stiffness in mesenchymal stem cells. In addition, the results also showed the involvement of SORBS1 in stiffness-dependent regulation into adipocyte differentiation. We also identified a second vinculin-binding site in SORBS3 and demonstrated its importance using biochemical analysis.

Free Research Field

応用分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

細胞外基質の硬さは間葉系幹細胞の脂肪細胞や骨芽細胞への分化制御に深く関与している。このため、今回の研究成果は間葉系幹細胞を利用した再生医療を発展させるための重要な知見を提供する。また組織の硬さはがんの悪性化にも関わっているため、本研究はがんの悪性化の仕組みの解明にも貢献できる。