A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Vimentin regulates Notch signaling strength and arterial remodeling in response to hemodynamic stress
Tekijät: Nicole C . A. van Engeland, Freddy Suarez Rodriguez, Adolfo Rivero-Müller, Tommaso Ristori, Camille L. Duran, Oscar M. J. A. Stassen, Daniel Antfolk, Rob C. H. Driessen, Saku Ruohonen, Suvi T. Ruohonen, Salla Nuutinen,
Eriika Savontaus, Sandra Loerakker, Kayla J. Bayless, Marika Sjöqvist, Carlijn V. C . Bouten, John E. Eriksson, Cecilia M. Sahlgren
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2019
Journal: Scientific Reports
Tietokannassa oleva lehden nimi: SCIENTIFIC REPORTS
Lehden akronyymi: SCI REP-UK
Artikkelin numero: ARTN 12415
Vuosikerta: 9
Sivujen määrä: 14
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-019-48218-w
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/42519087
The intermediate filament (IF) cytoskeleton has been proposed to regulate morphogenic processes by integrating the cell fate signaling machinery with mechanical cues. Signaling between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) through the Notch pathway regulates arterial remodeling in response to changes in blood flow. Here we show that the IF-protein vimentin regulates Notch signaling strength and arterial remodeling in response to hemodynamic forces. Vimentin is important for Notch transactivation by ECs and vimentin knockout mice (VimKO) display disrupted VSMC differentiation and adverse remodeling in aortic explants and in vivo. Shear stress increases Jagged1 levels and Notch activation in a vimentin-dependent manner. Shear stress induces phosphorylation of vimentin at serine 38 and phosphorylated vimentin interacts with Jagged1 and increases Notch activation potential. Reduced Jagged1-Notch transactivation strength disrupts lateral signal induction through the arterial wall leading to adverse remodeling. Taken together we demonstrate that vimentin forms a central part of a mechanochemical transduction pathway that regulates multilayer communication and structural homeostasis of the arterial wall.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
