Nature Communications (Aug 2019)
WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling
- Huimei Chen,
- Aida Moreno-Moral,
- Francesco Pesce,
- Nithya Devapragash,
- Massimiliano Mancini,
- Ee Ling Heng,
- Maxime Rotival,
- Prashant K. Srivastava,
- Nathan Harmston,
- Kirill Shkura,
- Owen J. L. Rackham,
- Wei-Ping Yu,
- Xi-Ming Sun,
- Nicole Gui Zhen Tee,
- Elisabeth Li Sa Tan,
- Paul J. R. Barton,
- Leanne E. Felkin,
- Enrique Lara-Pezzi,
- Gianni Angelini,
- Cristina Beltrami,
- Michal Pravenec,
- Sebastian Schafer,
- Leonardo Bottolo,
- Norbert Hubner,
- Costanza Emanueli,
- Stuart A. Cook,
- Enrico Petretto
Affiliations
- Huimei Chen
- Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School
- Aida Moreno-Moral
- Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School
- Francesco Pesce
- Department of Emergency and Organ Transplantation (DETO), University of Bari
- Nithya Devapragash
- Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School
- Massimiliano Mancini
- SOC di Anatomia Patologica, Ospedale San Giovanni di Dio
- Ee Ling Heng
- National Heart and Lung Institute, Imperial College London
- Maxime Rotival
- Unit of Human Evolutionary Genetics, Institute Pasteur
- Prashant K. Srivastava
- Division of Brain Sciences, Imperial College Faculty of Medicine
- Nathan Harmston
- Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School
- Kirill Shkura
- Division of Brain Sciences, Imperial College Faculty of Medicine
- Owen J. L. Rackham
- Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School
- Wei-Ping Yu
- Animal Gene Editing Laboratory, BRC
- Xi-Ming Sun
- MRC London Institute of Medical Sciences (LMC), Imperial College
- Nicole Gui Zhen Tee
- National Heart Centre Singapore
- Elisabeth Li Sa Tan
- Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School
- Paul J. R. Barton
- National Heart and Lung Institute, Imperial College London
- Leanne E. Felkin
- National Heart and Lung Institute, Imperial College London
- Enrique Lara-Pezzi
- Centro Nacional de Investigaciones Cardiovasculares – CNIC
- Gianni Angelini
- National Heart and Lung Institute, Imperial College London
- Cristina Beltrami
- National Heart and Lung Institute, Imperial College London
- Michal Pravenec
- Institute of Physiology, Czech Academy of Sciences
- Sebastian Schafer
- Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School
- Leonardo Bottolo
- Department of Medical Genetics, University of Cambridge
- Norbert Hubner
- Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
- Costanza Emanueli
- National Heart and Lung Institute, Imperial College London
- Stuart A. Cook
- Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School
- Enrico Petretto
- Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School
- DOI
- https://doi.org/10.1038/s41467-019-11551-9
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 19
Abstract
Pathological cardiac fibrosis is a hallmark of diseases leading to heart failure. Here, the authors used systems genetics to identify a pro-fibrotic gene network regulated by WWP2, a E3 ubiquitin ligase, which orchestrates the nucleocytoplasmic shuttling and transcriptional activity of SMAD2 in the diseased heart.
