Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP in the vascular remodeling.
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Aorta
/ growth & development
Carotid Arteries
/ growth & development
Cellular Microenvironment
/ genetics
Extracellular Matrix
/ genetics
Focal Adhesions
/ genetics
Hippo Signaling Pathway
Humans
Integrin beta1
/ genetics
Mechanotransduction, Cellular
Mice
Neointima
/ genetics
Protein Serine-Threonine Kinases
/ genetics
Signal Transduction
/ genetics
Thrombospondin 1
/ genetics
Transcription Factors
/ genetics
Vascular Remodeling
/ genetics
YAP-Signaling Proteins
rap GTP-Binding Proteins
/ genetics
YAP
extracellular matrix (ECM)
mechanotransduction
thrombospondin-1
vessel remodeling
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
05 05 2020
05 05 2020
Historique:
pubmed:
24
4
2020
medline:
29
7
2020
entrez:
24
4
2020
Statut:
ppublish
Résumé
The extracellular matrix (ECM) initiates mechanical cues that activate intracellular signaling through matrix-cell interactions. In blood vessels, additional mechanical cues derived from the pulsatile blood flow and pressure play a pivotal role in homeostasis and disease development. Currently, the nature of the cues from the ECM and their interaction with the mechanical microenvironment in large blood vessels to maintain the integrity of the vessel wall are not fully understood. Here, we identified the matricellular protein thrombospondin-1 (Thbs1) as an extracellular mediator of matrix mechanotransduction that acts via integrin αvβ1 to establish focal adhesions and promotes nuclear shuttling of Yes-associated protein (YAP) in response to high strain of cyclic stretch. Thbs1-mediated YAP activation depends on the small GTPase Rap2 and Hippo pathway and is not influenced by alteration of actin fibers. Deletion of
Identifiants
pubmed: 32321834
pii: 1919702117
doi: 10.1073/pnas.1919702117
pmc: PMC7211957
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Integrin beta1
0
Thrombospondin 1
0
Transcription Factors
0
YAP-Signaling Proteins
0
YAP1 protein, human
0
thrombospondin-1, human
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
RAP2A protein, human
EC 3.6.1.-
rap GTP-Binding Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9896-9905Déclaration de conflit d'intérêts
The authors declare no competing interest.
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