PXD030493

PXD030493 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling of hCMEC/D3 cells exposed 3 days to laminar physiological shear stress
Description	Endothelial cells (ECs) are constantly submitted in vivo to hemodynamical forces derived from the blood circulation, including shear stress (SS). EC are able to detect SS and consequently adapt their phenotype, thus affecting many endothelial functions. If a plethora of shear stress-regulated molecular networks have been described in peripheral EC, less is known about the molecular responses of microvascular brain ECs which constitute the blood-brain barrier (BBB). In this work, we investigated the response of human cerebral microvascular ECs to laminar physiological shear stress using the well characterized hCMEC/D3 cell line. Interestingly, we showed that hCMEC/D3 cells responded to shear stress by aligning perpendicularly to the flow direction, contrary to peripheral endothelial cells which aligned in the flow direction. Whole proteomic profiles were compared between hCMEC/D3 cells cultured either in static condition or under 5 or 10 dyn.cm-2 SS for three days. 3592 proteins were identified and expression levels were significantly affected for 3% of them upon both SS conditions. Pathway analyses were performed which revealed that most proteins overexpressed by SS refer to the antioxidant defense, probably mediated by activation of the NRF2 transcriptional factor. Regarding down-regulated proteins, most of them participate to the pro-inflammatory response, cell motility and proliferation. These findings confirm the induction of EC quiescence by laminar physiological SS and reveal a strong neuroprotective effect of SS on hCMEC/D3 cells, suggesting a similar effect on the BBB. Our results also showed that SS did not significantly increase expression levels nor did it affect the localization of junctional proteins or the functional activity of several ABC transporters (P-glycoprotein and MRPs). This work provides new insights on the response of microvascular brain EC to SS and on the importance of SS for optimizing in vitro BBB models.
HostingRepository	PRIDE
AnnounceDate	2022-08-12
AnnouncementXML	Submission_2022-08-12_00:36:52.690.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	François GUILLONNEAU
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-17 13:19:35	ID requested
⏵ 1	2022-08-12 00:36:53	announced

Choublier N, Taghi M, Menet MC, Le Gall M, Bruce J, Chafey P, Guillonneau F, Moreau A, Denizot C, Parmentier Y, Nakib S, Borderie D, Bouzinba-Segard H, Couraud PO, Bourdoulous S, Decl, è, ves X, Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses. Fluids Barriers CNS, 19(1):41(2022) [pubmed]

submitter keyword: Q-exactive

Endothelial cells

bottom up LFQ proteomics

shear stress

blood-brain barrier

brain microvessels

Xavier Decleves
contact affiliation	Université de Paris, Inserm, UMRS-1144 Optimisation Thérapeutique en Neuropsychopharmacologie
contact email	xavier.decleves@u-paris.fr
lab head
François GUILLONNEAU
contact affiliation	3P5 Université de Paris
contact email	francois.guillonneau@parisdescartes.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/08/PXD030493

PRIDE project URI

• PRIDE
  1. PXD030493
     1. Label: PRIDE project
     2. Name: Proteomic profiling of hCMEC/D3 cells exposed 3 days to laminar physiological shear stress