PXD014526

PXD014526 is an original dataset announced via ProteomeXchange.

Title	Flow-induced reorganization of laminin-integrin networks within the endothelial basement membrane uncovered by proteomics
Description	Objective The vessel wall is continuously exposed to hemodynamic forces generated by blood flow. Endothelial mechanosensors perceive and translate mechanical signals via cellular signaling pathways into biological processes that control endothelial development, phenotype and function. Here, we aim to unravel the molecular mechanisms underlying endothelial mechanosensing. Approach and results We applied a quantitative mass spectrometry approach combined with cell surface chemical footprinting to assess the hemodynamic effects on the endothelium on a system-wide level. These studies revealed that of the >5000 quantified proteins 104 were altered, which were highly enriched for extracellular matrix proteins and proteins involved in cell-matrix adhesion. Cell surface proteomics furthermore indicated that LAMA4 was proteolytically processed upon flow-exposure, which corresponded to the decreased LAMA4 mass observed on immunoblot. Immunofluorescence microscopy studies highlighted that the endothelial basement membrane was drastically remodeled upon flow exposure. We observed a network-like pattern of LAMA4 and LAMA5, which corresponded to the localization of laminin-adhesion molecules ITGA6 and ITGB4. Furthermore, the adaptation to flow-exposure did not affect the inflammatory response to tumor necrosis factor α, indicating that inflammation and flow trigger fundamentally distinct endothelial signaling pathways with limited reciprocity and synergy. Conclusions Taken together, this study uncovers the blood flow-induced remodeling of the basement membrane and stresses the importance of the subendothelial basement membrane in vascular homeostasis.
HostingRepository	PRIDE
AnnounceDate	2020-04-29
AnnouncementXML	Submission_2020-04-29_04:28:46.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eelke Béguin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-09 01:51:09	ID requested
⏵ 1	2020-04-29 04:28:48	announced

B, é, guin EP, Janssen EFJ, Hoogenboezem M, Meijer AB, Hoogendijk AJ, van den Biggelaar M, Flow-induced Reorganization of Laminin-integrin Networks Within the Endothelial Basement Membrane Uncovered by Proteomics. Mol Cell Proteomics, 19(7):1179-1192(2020) [pubmed]

submitter keyword: Endothelium, flow, shear stress, proteomics, extracellular matrix, basement membrane, integrin, laminin, TNFα, inflammation

Maartje van den Biggelaar
contact affiliation	Department of Molecular and Cellular Hemostasis, Sanquin Research, Amsterdam, 1066CX, The Netherlands
contact email	m.vandenbiggelaar@sanquin.nl
lab head
Eelke Béguin
contact affiliation	Sanquin Research
contact email	e.beguin@sanquin.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014526
     1. Label: PRIDE project
     2. Name: Flow-induced reorganization of laminin-integrin networks within the endothelial basement membrane uncovered by proteomics