Notch signaling regulates strain-mediated phenotypic switching of vascular smooth muscle cells

Autor: Cansu Karakaya, Mark C. van Turnhout, Valery L. Visser, Tommaso Ristori, Carlijn V. C. Bouten, Cecilia M. Sahlgren, Sandra Loerakker
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Cell and Developmental Biology, Vol 10 (2022)
Druh dokumentu: article
ISSN: 2296-634X
DOI: 10.3389/fcell.2022.910503
Popis: Mechanical stimuli experienced by vascular smooth muscle cells (VSMCs) and mechanosensitive Notch signaling are important regulators of vascular growth and remodeling. However, the interplay between mechanical cues and Notch signaling, and its contribution to regulate the VSMC phenotype are still unclear. Here, we investigated the role of Notch signaling in regulating strain-mediated changes in VSMC phenotype. Synthetic and contractile VSMCs were cyclically stretched for 48 h to determine the temporal changes in phenotypic features. Different magnitudes of strain were applied to investigate its effect on Notch mechanosensitivity and the phenotypic regulation of VSMCs. In addition, Notch signaling was inhibited via DAPT treatment and activated with immobilized Jagged1 ligands to understand the role of Notch on strain-mediated phenotypic changes of VSMCs. Our data demonstrate that cyclic strain induces a decrease in Notch signaling along with a loss of VSMC contractile features. Accordingly, the activation of Notch signaling during cyclic stretching partially rescued the contractile features of VSMCs. These findings demonstrate that Notch signaling has an important role in regulating strain-mediated phenotypic switching of VSMCs.
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