PXD022212 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-10-28 01:14:29 | ID requested | |
⏵ 1 | 2021-03-23 11:53:11 | announced | |
Publication List
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] |
Keyword List
submitter keyword: Cardiomyocytes, angiogenesis, ischemic injury, ZEB2 |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD022212
- Label: PRIDE project
- Name: ZEB2 protects the heart from ischemic damage