PXD033549

PXD033549 is an original dataset announced via ProteomeXchange.

Title	Endothelial senescence mediates hypoxia-induced vascular remodeling by modulating PDGFB expression
Description	Uncontrolled accumulation of pulmonary artery smooth muscle cells (PASMC) to the distal pulmonary arterioles (PAs) is one of the major characteristics of pulmonary hypertension (PH). Cellular senescence contributes to aging and lung diseases associated with PH and links to PH progression. However, the mechanism by which cellular senescence controls vascular remodeling in PH is not fully understood. The levels of senescence marker, p16INK4A and senescence-associated β-galactosidase (SA-β-gal) activity are higher in PA endothelial cells (ECs) isolated from idiopathic pulmonary arterial hypertension (IPAH) patients compared to those from healthy individuals. Hypoxia-induced accumulation of α-smooth muscle actin (αSMA)-positive cells to the PAs is attenuated in p16fl/fl-Cdh5(PAC)-CreERT2 (p16iΔEC) mice after tamoxifen induction. We have reported that endothelial TWIST1 mediates hypoxia-induced vascular remodeling by increasing platelet-derived growth factor (PDGFB) expression. Transcriptomic analyses of IPAH patient or hypoxia-induced mouse lung ECs reveal the alteration of senescence-related gene expression and their interaction with TWIST1. Knockdown of p16INK4A attenuates the expression of PDGFB and TWIST1 in IPAH patient PAECs or hypoxia-treated mouse lungs and suppresses accumulation of αSMA–positive cells to the supplemented ECs in the gel implanted on the mouse lungs. Hypoxia-treated mouse lung EC-derived exosomes stimulate DNA synthesis and migration of PASMCs in vitro and in the gel implanted on the mouse lungs, while p16iΔEC mouse lung EC-derived exosomes inhibit the effects. These results suggest that endothelial senescence controls αSMA–positive cell proliferation and migration in PH through TWIST1-PDGFB signaling.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:32:50.422.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD033549
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Priscilla Kyi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-28 02:29:57	ID requested
1	2022-10-14 20:50:37	announced
⏵ 2	2023-11-14 08:32:52	announced	2023-11-14: Updated project metadata.

10.6019/PXD033549;

Kyi P, Hendee K, Hunyenyiwa T, Matus K, Mammoto T, Mammoto A, Endothelial senescence mediates hypoxia-induced vascular remodeling by modulating PDGFB expression. Front Med (Lausanne), 9():908639(2022) [pubmed]

submitter keyword: TWIST1,pulmonary hypertension, hypoxia, endothelial cell, PDGFB, senescence

Akiko Mammoto
contact affiliation	Department of Pediatrics, Department of Cell Biology, Neurobiology and Anatomy Medical College of Wisconsin, Milwaukee, WI, United States
contact email	amammoto@mcw.edu
lab head
Priscilla Kyi
contact affiliation	Medical College of Wisconsin
contact email	pkyi@mcw.edu
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/2022/10/PXD033549

PRIDE project URI

• PRIDE
  1. PXD033549
     1. Label: PRIDE project
     2. Name: Endothelial senescence mediates hypoxia-induced vascular remodeling by modulating PDGFB expression