Imperial College London
Alternate

ProfessorJorgeFerrer

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Chair in Medicine and Genetics
 
 
 
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Contact

 

+44 (0)20 7594 0968j.ferrer

 
 
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Location

 

535ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Palomer:2020:10.1038/s41392-020-0114-1,
author = {Palomer, X and Silvia, Roman-Azcona M and Pizarro-Delgado, J and Planavila, A and Villarroya, F and Valenzuela-Alcaraz, B and Crispi, F and Sepulveda-Martinez, A and Miguel-Escalada, I and Ferrer, J and Francisco, Nistal J and Garcia, R and Davidson, MM and Barroso, E and Vazquez-Carrera, M},
doi = {10.1038/s41392-020-0114-1},
journal = {Signal Transduction and Targeted Therapy},
pages = {1--10},
title = {SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation},
url = {http://dx.doi.org/10.1038/s41392-020-0114-1},
volume = {5},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Sirtuin 3 (SIRT3) is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress. Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances. In this study, we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells. SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1. Consistent with this, SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α. Notably, these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1. Finally, we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter. These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway. Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy, heart failure, and diabetic cardiomyopathy, our results point to SIRT3 as a potential target for treating these diseases.
AU  - Palomer,X
AU  - Silvia,Roman-Azcona M
AU  - Pizarro-Delgado,J
AU  - Planavila,A
AU  - Villarroya,F
AU  - Valenzuela-Alcaraz,B
AU  - Crispi,F
AU  - Sepulveda-Martinez,A
AU  - Miguel-Escalada,I
AU  - Ferrer,J
AU  - Francisco,Nistal J
AU  - Garcia,R
AU  - Davidson,MM
AU  - Barroso,E
AU  - Vazquez-Carrera,M
DO  - 10.1038/s41392-020-0114-1
EP  - 10
PY  - 2020///
SN  - 2095-9907
SP  - 1
TI  - SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation
T2  - Signal Transduction and Targeted Therapy
UR  - http://dx.doi.org/10.1038/s41392-020-0114-1
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000530070000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41392-020-0114-1
UR  - http://hdl.handle.net/10044/1/79328
VL  - 5
ER  -
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