PXD051197

PXD051197 is an original dataset announced via ProteomeXchange.

Title	Distinct phenotypes induced by acute hypoxia and TGF-β1 in human adult cardiac fibroblasts
Description	Myocardial infarctions cause hypoxic injury to downstream tissue and a consequent fibrotic remodeling process to replace injured tissue with a scar. Scar formation occurs through phases of wound healing in which stimuli such as transforming growth factor-beta (TGF-β) drive cardiac fibroblasts to activate into a myofibroblast phenotype and deposit matrix molecules that form a scar. While this is necessary to repair injured tissue, excessive fibrosis commonly occurs which is correlated with heart failure. Therefore, defining cardiac fibroblast phenotypes under hypoxic stimuli and TGF-β is essential for understanding and treating pathological fibrosis. We robustly characterized fibroblast phenotype through immunofluorescence, quantitative RT-PCR, and proteomic analysis, after either TGF-β treatment or hypoxia durations that mimic acute hypoxic injury post-infarction. We find that hypoxic fibroblasts respond to low oxygen with increased hypoxia inducible factor 1 (HIF-1) but not HIF-2 activity by 4h. This is accompanied by increased gene and protein levels of VEGFA and LOX, respectively, which are both targets of HIF-1. Both TGF-β1 and hypoxia inhibit proliferation by 24h. While TGF-β1 treatment upregulated various fibrotic pathways, hypoxia causes a global reduction in protein synthesis, including collagen biosynthesis. This study discerns overlapping from distinctive outcomes of TGF-β1 and hypoxia treatment, which is important for elucidating their roles in fibrotic remodeling post-MI.
HostingRepository	PRIDE
AnnounceDate	2024-07-03
AnnouncementXML	Submission_2024-07-03_09:34:36.032.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sarah Parker
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-04 09:55:39	ID requested
⏵ 1	2024-07-03 09:34:36	announced

Dataset with its publication pending

submitter keyword: hypoxia, transforming growth factor-beta, cardiac fibrosis, hypoxia-inducible factors, myocardial infarction

Megan McCain
contact affiliation	Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089, USA Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, Los Angeles, CA, 90033, USA
contact email	mlmccain@usc.edu
lab head
Sarah Parker
contact affiliation	Cedars-Sinai Medical Center
contact email	sarah.parker@cshs.org
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/2024/07/PXD051197

PRIDE project URI

• PRIDE
  1. PXD051197
     1. Label: PRIDE project
     2. Name: Distinct phenotypes induced by acute hypoxia and TGF-β1 in human adult cardiac fibroblasts