A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
A noncanonical role for Jagged1 in endothelial mechanotransduction
Tekijät: Suarez Rodriguez, Freddy; Virtanen, Noora; Kiviluoto, Elmeri; Driessen, Rob C. H.; Zhao, Feihu; Bouten, Carlijn V. C.; Stassen, Oscar M. J. A.; Sahlgren, Cecilia M.
Kustantaja: Wiley
Julkaisuvuosi: 2026
Lehti: FEBS Journal
ISSN: 1742-464X
eISSN: 1742-4658
DOI: https://doi.org/10.1111/febs.70466
Julkaisun avoimuus kirjaamishetkellä: Avoimesti saatavilla
Julkaisukanavan avoimuus : Osittain avoin julkaisukanava
Verkko-osoite: https://doi.org/10.1111/febs.70466
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/515747867
Rinnakkaistallenteen lisenssi: CC BY
Rinnakkaistallennetun julkaisun versio: Kustantajan versio
The Notch signaling pathway plays a crucial role in regulating endothelial biology. Notch signaling is sensitive to hemodynamic forces and governs mechanically driven cardiovascular development, physiology, and remodeling. However, the mechanisms by which mechanical forces integrate with the Notch pathway remain largely unknown. Here, we uncover a noncanonical role for the Notch ligand protein jagged-1 (Jagged1) in regulating the activity of mechanosensitive kinases in endothelial cells. We show that shear stress induces expression and relocalization of Jagged1 to cell junctions downstream of flow. Jagged1 expression under stress demonstrates magnitude dependence, and peaks at 0.8–1 Pa without impacting the Notch-activation potential of Jagged1. Jagged1 also regulates the activity of mechanosensitive kinases. Deletion of Jagged1 reduces the activity of vascular endothelial growth factor receptor 2 (VEGFR2) and mitogen-activated protein kinase (ERK) in vitro and diminished ERK activity in zebrafish embryos without affecting canonical Notch signaling. Furthermore, direct physical stimulation of Jagged1 using antibody-conjugated beads triggers the activation of VEGFR2 and ERK, mediated by Jagged1-induced proto-oncogene tyrosine-protein kinase Src activation. Taken together, we demonstrate a previously unknown noncanonical role for Jagged1 as a regulator of the activity of pathways involved in endothelial mechanotransduction.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
Julkaisussa olevat rahoitustiedot:
This project has received funding from the following sources: European Research Council (ERC) ERC-CoG No 771168 (ForceMorph). European Research Council (ERC) ERC-SynG No 101167065 (Making Blood). Research Council of Finland, Center of Excellence, decision number #374179 (CoEIMMENs). Research Council of Finland, decision number #316882 (SPACE). Research Council of Finland, decision number #330411 (SignalSheets). Research Council of Finland, decision number #336355 (Solutions for Health at Åbo Akademi University). Research Council of Finland, decision number #337531 and #357911 (InFLAMES Flagship Program). Åbo Akademi University Foundation's Centers of Excellence in Cellular Mechanostasis (CellMech) and Bioelectronic Activation of Cell Functions (BACE). The work performed by FSR has been partially funded by personal grants from The Swedish Cultural Foundation in Finland, Instrumentarium Science Foundation and Magnus Ehrnrooth Foundation.
Open access publishing facilitated by Abo Akademi, as part of the Wiley - FinELib agreement.
