PXD022212

PXD022212 is an original dataset announced via ProteomeXchange.

Title	ZEB2 protects the heart from ischemic damage
Description	infarct size and subsequent deterioration in function. The identification of factors that enhance cardiac repair by the restoration of the vascular network is, therefore, of great significance. Here, we show that the transcription factor Zinc finger E-box-binding homeobox 2 (ZEB2) is increased in stressed cardiomyocytes and induces a cardioprotective cross-talk between cardiomyocytes and endothelial cells to enhance angiogenesis after ischemia. Single-cell sequencing indicates ZEB2 to be enriched in injured cardiomyocytes. Cardiomyocyte-specific deletion of ZEB2 results in impaired cardiac contractility and infarct healing post-myocardial infarction (post-MI), while cardiomyocyte-specific ZEB2 overexpression improves cardiomyocyte survival and cardiac function. We identified Thymosin 4 (TMSB4) and Prothymosin  (PTMA) as main paracrine factors released from cardiomyocytes to stimulate angiogenesis by enhancing endothelial cell migration, and whose regulation is validated in our in vivo models. Therapeutic delivery of ZEB2 to cardiomyocytes in the infarcted heart induces the expression of TMSB4 and PTMA, which enhances angiogenesis and prevents cardiac dysfunction. These findings reveal ZEB2 as a beneficial factor during ischemic injury, which may hold promise for the identification of new therapies.
HostingRepository	PRIDE
AnnounceDate	2021-03-23
AnnouncementXML	Submission_2021-03-23_11:53:10.905.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Harmjan Vos
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-28 01:14:29	ID requested
⏵ 1	2021-03-23 11:53:11	announced

Gladka MM, Kohela A, Molenaar B, Versteeg D, Kooijman L, Monshouwer-Kloots J, Kremer V, Vos HR, Huibers MMH, Haigh JJ, Huylebroeck D, Boon RA, Giacca M, van Rooij E, Cardiomyocytes stimulate angiogenesis after ischemic injury in a ZEB2-dependent manner. Nat Commun, 12(1):84(2021) [pubmed]

submitter keyword: Cardiomyocytes, angiogenesis, ischemic injury, ZEB2

Eva van Rooij
contact affiliation	Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Centre, Utrecht, The Netherlands
contact email	e.vanrooij@hubrecht.eu
lab head
Harmjan Vos
contact affiliation	University Medical Center Utrecht Dept. Molecular Cancer Research
contact email	h.r.vos-3@umcutrecht.nl
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/2021/03/PXD022212

PRIDE project URI

• PRIDE
  1. PXD022212
     1. Label: PRIDE project
     2. Name: ZEB2 protects the heart from ischemic damage