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PXD051197

PXD051197 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDistinct phenotypes induced by acute hypoxia and TGF-β1 in human adult cardiac fibroblasts
DescriptionMyocardial 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.
HostingRepositoryPRIDE
AnnounceDate2024-07-03
AnnouncementXMLSubmission_2024-07-03_09:34:36.032.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSarah Parker
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-04-04 09:55:39ID requested
12024-07-03 09:34:36announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: hypoxia, transforming growth factor-beta, cardiac fibrosis, hypoxia-inducible factors, myocardial infarction
Contact List
Megan McCain
contact affiliationAlfred 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 emailmlmccain@usc.edu
lab head
Sarah Parker
contact affiliationCedars-Sinai Medical Center
contact emailsarah.parker@cshs.org
dataset submitter
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Dataset FTP location
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