WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00507837" target="_blank" >RIV/67985823:_____/19:00507837 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1038/s41467-019-11551-9" target="_blank" >https://doi.org/10.1038/s41467-019-11551-9</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-019-11551-9" target="_blank" >10.1038/s41467-019-11551-9</a>

Result language
angličtina
Original language name
WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling
Original language description
Cardiac fibrosis is a final common pathology in inherited and acquired heart diseases that causes cardiac electrical and pump failure. Here, we use systems genetics to identify a pro-fibrotic gene network in the diseased heart and show that this network is regulated by the E3 ubiquitin ligase WWP2, specifically by the WWP2-N terminal isoform. Importantly, the WWP2-regulated pro-fibrotic gene network is conserved across different cardiac diseases characterized by fibrosis: human and murine dilated cardiomyopathy and repaired tetralogy of Fallot. Transgenic mice lacking the N-terminal region of the WWP2 protein show improved cardiac function and reduced myocardial fibrosis in response to pressure overload or myocardial infarction. In primary cardiac fibroblasts, WWP2 positively regulates the expression of pro-fibrotic markers and extracellular matrix genes. TGF beta 1 stimulation promotes nuclear translocation of the WWP2 isoforms containing the N-terminal region and their interaction with SMAD2. WWP2 mediates the TGF beta 1-induced nucleocytoplasmic shuttling and transcriptional activity of SMAD2.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30201 - Cardiac and Cardiovascular systems

Project
<a href="/en/project/GB14-36804G" target="_blank" >GB14-36804G: Centre of mitochondrial biology and pathology (MITOCENTRE)</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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