TY - JOUR
T1 - Mechanical loading of intraluminal pressure mediates wound angiogenesis by regulating the TOCA family of F-BAR proteins
AU - Yuge, Shinya
AU - Nishiyama, Koichi
AU - Arima, Yuichiro
AU - Hanada, Yasuyuki
AU - Oguri-Nakamura, Eri
AU - Hanada, Sanshiro
AU - Ishii, Tomohiro
AU - Wakayama, Yuki
AU - Hasegawa, Urara
AU - Tsujita, Kazuya
AU - Yokokawa, Ryuji
AU - Miura, Takashi
AU - Itoh, Toshiki
AU - Tsujita, Kenichi
AU - Mochizuki, Naoki
AU - Fukuhara, Shigetomo
N1 - Funding Information:
We thank N. Lawson (University of Massachusetts Medical School) for the plasmid encoding the fli1 promoter and Tg(fli1:GFP)y1fish, D. Y. Stainier (Max Planck Institute for Heart and Lung Research) for Tg(kdrl:EGFP)s843, K. Kawakami (National Institute of Genetics) for the Tol2 system, H. Miyoshi (BioResource Center, RIKEN) for the CSII-CMV-MCS-IRES2-Bsd lentiviral expression vector and the packaging plasmids, S. Higashiyama (Ehime University) for the lentiviral expression vector encoding Azami-Green, and N. Suzuki (Kanazawa University) for sharing the experimental protocol for immunohistochemistry of fish skin. We are grateful to the Imaging Core Laboratory, The Institute of Medical Science, The University of Tokyo, and Nikon Instruments Inc. for helping with the A1R MP+ multiphoton confocal microscope and image acquisition and to Olympus Corporation and the University of Tokyo IMCB Olympus Bioimaging Center for helping with the FluoView FVMPE-RS multiphoton microscope and image acquisition. We also thank K. Ando and H. Nakajima for advice on in vivo experiments and hemodynamic analysis, respectively, and H. Ichimiya, S. Egawa, K. Kato, K. Hiratomi, M. Sone, W. Koeda, M. Uchikawa, and C. Esumi for excellent technical assistance. This work was supported by a grant from the Japan Agency for Medical Research and Development (AMED) under Grant Number JP17gm5810010 to S.F. and by Core Research for Evolutional Science and Technology (CREST) from Japan Science and Technology (JST) under Grant Number JPMJCR14W4 to K.N., R.Y., and T.M.; by Grants-in-Aid for Scientific Research (B) to S.F. (16H05125, 21H02665) and K.N. (19H04446), for Exploratory Research to S.F. (17K19689, 19K22517, 21K19358) and K.N. (26670394), for Scientific Research for Young Scientists to S.Y. (17K15565), for Scientific Research (C) to S.Y. (19K07307) and K.N. (16KT0173) from the Japan Society for the Promotion of Science; research grants from Takeda Science Foundation to S.F., from the Naito Foundation to S.F., from Daiichi Sankyo Foundation of Life Science to S.F., from Astellas Foundation for Research on Metabolic Disorders to S.F. and K.N., from the Princess Takamatsu Cancer Research Fund to S.F., from The NOVARTIS Foundation (Japan) for the Promotion of Science to S.F. and K.N., from The Uehara Memorial Foundation to S.F., from the TERUMO LIFE SCIENCE FOUNDATION to S.F., from SENSHIN Medical Research Foundation to K.N., and from the NAKATANI FOUNDATION for advancement of measuring technologies in biomedical engineering to K.N.
Funding Information:
We thank N. Lawson (University of Massachusetts Medical School) for the plasmid encoding the fli1 promoter and Tg(fli1:GFP) fish, D. Y. Stainier (Max Planck Institute for Heart and Lung Research) for Tg(kdrl:EGFP), K. Kawakami (National Institute of Genetics) for the Tol2 system, H. Miyoshi (BioResource Center, RIKEN) for the CSII-CMV-MCS-IRES2-Bsd lentiviral expression vector and the packaging plasmids, S. Higashiyama (Ehime University) for the lentiviral expression vector encoding Azami-Green, and N. Suzuki (Kanazawa University) for sharing the experimental protocol for immunohistochemistry of fish skin. We are grateful to the Imaging Core Laboratory, The Institute of Medical Science, The University of Tokyo, and Nikon Instruments Inc. for helping with the A1R MP+ multiphoton confocal microscope and image acquisition and to Olympus Corporation and the University of Tokyo IMCB Olympus Bioimaging Center for helping with the FluoView FVMPE-RS multiphoton microscope and image acquisition. We also thank K. Ando and H. Nakajima for advice on in vivo experiments and hemodynamic analysis, respectively, and H. Ichimiya, S. Egawa, K. Kato, K. Hiratomi, M. Sone, W. Koeda, M. Uchikawa, and C. Esumi for excellent technical assistance. This work was supported by a grant from the Japan Agency for Medical Research and Development (AMED) under Grant Number JP17gm5810010 to S.F. and by Core Research for Evolutional Science and Technology (CREST) from Japan Science and Technology (JST) under Grant Number JPMJCR14W4 to K.N., R.Y., and T.M.; by Grants-in-Aid for Scientific Research (B) to S.F. (16H05125, 21H02665) and K.N. (19H04446), for Exploratory Research to S.F. (17K19689, 19K22517, 21K19358) and K.N. (26670394), for Scientific Research for Young Scientists to S.Y. (17K15565), for Scientific Research (C) to S.Y. (19K07307) and K.N. (16KT0173) from the Japan Society for the Promotion of Science; research grants from Takeda Science Foundation to S.F., from the Naito Foundation to S.F., from Daiichi Sankyo Foundation of Life Science to S.F., from Astellas Foundation for Research on Metabolic Disorders to S.F. and K.N., from the Princess Takamatsu Cancer Research Fund to S.F., from The NOVARTIS Foundation (Japan) for the Promotion of Science to S.F. and K.N., from The Uehara Memorial Foundation to S.F., from the TERUMO LIFE SCIENCE FOUNDATION to S.F., from SENSHIN Medical Research Foundation to K.N., and from the NAKATANI FOUNDATION for advancement of measuring technologies in biomedical engineering to K.N. y1 s843
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Angiogenesis is regulated in coordinated fashion by chemical and mechanical cues acting on endothelial cells (ECs). However, the mechanobiological mechanisms of angiogenesis remain unknown. Herein, we demonstrate a crucial role of blood flow-driven intraluminal pressure (IP) in regulating wound angiogenesis. During wound angiogenesis, blood flow-driven IP loading inhibits elongation of injured blood vessels located at sites upstream from blood flow, while downstream injured vessels actively elongate. In downstream injured vessels, F-BAR proteins, TOCA1 and CIP4, localize at leading edge of ECs to promote N-WASP-dependent Arp2/3 complex-mediated actin polymerization and front-rear polarization for vessel elongation. In contrast, IP loading expands upstream injured vessels and stretches ECs, preventing leading edge localization of TOCA1 and CIP4 to inhibit directed EC migration and vessel elongation. These data indicate that the TOCA family of F-BAR proteins are key actin regulatory proteins required for directed EC migration and sense mechanical cell stretching to regulate wound angiogenesis.
AB - Angiogenesis is regulated in coordinated fashion by chemical and mechanical cues acting on endothelial cells (ECs). However, the mechanobiological mechanisms of angiogenesis remain unknown. Herein, we demonstrate a crucial role of blood flow-driven intraluminal pressure (IP) in regulating wound angiogenesis. During wound angiogenesis, blood flow-driven IP loading inhibits elongation of injured blood vessels located at sites upstream from blood flow, while downstream injured vessels actively elongate. In downstream injured vessels, F-BAR proteins, TOCA1 and CIP4, localize at leading edge of ECs to promote N-WASP-dependent Arp2/3 complex-mediated actin polymerization and front-rear polarization for vessel elongation. In contrast, IP loading expands upstream injured vessels and stretches ECs, preventing leading edge localization of TOCA1 and CIP4 to inhibit directed EC migration and vessel elongation. These data indicate that the TOCA family of F-BAR proteins are key actin regulatory proteins required for directed EC migration and sense mechanical cell stretching to regulate wound angiogenesis.
UR - http://www.scopus.com/inward/record.url?scp=85130637603&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85130637603&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-30197-8
DO - 10.1038/s41467-022-30197-8
M3 - Article
C2 - 35551172
AN - SCOPUS:85130637603
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2594
ER -