PDGFR-β Signaling Regulates Cardiomyocyte Proliferation and Myocardial Regeneration

Cell Reports
Zhang YueYu Nie

Abstract

Platelet-derived growth factor receptor (PDGFR) signaling is involved in proliferation and survival in a wide array of cell types. The role of PDGFR signaling in heart regeneration is still unknown. We find that PDGFR-β signaling decreases in myocardium with age and that conditional activation PDGFR-β in cardiomyocytes promotes heart regeneration. Employing RNA sequencing, we show that the enhancer of zeste homolog 2 (Ezh2) can be upregulated by PDGFR-β signaling in primary cardiomyocytes. Conditional knockout of Ezh2 blocks cardiomyocyte proliferation and H3K27me3 modification during neonatal heart regeneration with Ink4a/Arf upregulation, even in mice with myocyte-specific conditional activation of PDGFR-β. We also show that PDGFR-β controls EZH2 expression via the phosphatidylinositol 3-kinase (PI3K)/p-Akt pathway in cardiomyocytes. Gene therapy with adeno-associated virus serotype 9 (AAV9) encoding activated PDGFR-β enhances adult heart regeneration and systolic function. Our data demonstrate that the PDGFR-β/EZH2 pathway is critical for promoting cardiomyocyte proliferation and heart regeneration, providing a potential target for cardiac repair.

References

Sep 1, 1992·Journal of Molecular and Cellular Cardiology·M H SoonpaaJ C Oberpriller
Jan 15, 1982·Biochemical and Biophysical Research Communications·A JohnssonA Wasteson
Mar 17, 1997·Biochemical and Biophysical Research Communications·M Lopez-IlasacaM A Heidaran
May 12, 2000·Nature Cell Biology·X LiU Eriksson
May 2, 2001·Nature Cell Biology·E BergstenU Eriksson
Dec 17, 2005·The Journal of Clinical Investigation·Patrick C H HsiehRichard T Lee
Sep 8, 2006·Nature·Janakiraman KrishnamurthyNorman E Sharpless
Dec 13, 2006·Journal of the American College of Cardiology·Pawel ZymekNikolaos G Frangogiannis
May 17, 2008·Genes & Development·Johanna AndraeChrister Betsholtz
Nov 26, 2008·Molecular Cell·Raphael MargueronDanny Reinberg
Apr 4, 2009·Science·Olaf BergmannJonas Frisén
Jan 15, 2010·The Journal of Clinical Investigation·Vishnu ChintalgattuAarif Y Khakoo
Mar 24, 2010·Journal of Molecular and Cellular Cardiology·Marius VantlerWolfram-H Zimmermann
Jul 7, 2010·Cell·Mark A Lemmon, Joseph Schlessinger
Sep 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jieun KimChing-Ling Lien
Feb 26, 2011·Science·Enzo R PorrelloHesham A Sadek
Jun 15, 2011·Developmental Cell·Lorin E Olson, Philippe Soriano
Jun 21, 2011·Journal of Molecular and Cellular Cardiology·Jianhu ZhangAarif Y Khakoo
Oct 8, 2011·PloS One·Diana S NascimentoPerpétua Pinto-do-Ó
Nov 19, 2011·EMBO Molecular Medicine·Matthew L Steinhauser, Richard T Lee
Dec 14, 2011·Circulation Research·Aibin HeWilliam T Pu
Dec 12, 2012·Nature·Samuel E SenyoRichard T Lee
Jan 18, 2014·Nature Protocols·Ahmed I MahmoudHesham A Sadek
Oct 7, 2014·Journal of Cellular and Molecular Medicine·Liu RuiHu Shengshou
Dec 5, 2015·Cell Research·Qiaozhen LiuBin Zhou
Feb 6, 2016·Nature Medicine·Kimberly H Kim, Charles W M Roberts
Jan 6, 2017·EMBO Molecular Medicine·Mona Malek MohammadiJoerg Heineke

❮ Previous
Next ❯

Citations

Apr 29, 2020·Journal of Cellular and Molecular Medicine·Yandong LiYu Nie
Feb 15, 2020·Cellular & Molecular Immunology·Yandong LiYu Nie
Apr 29, 2020·Gene Therapy·Jiali DengJunjie Xiao
Jun 23, 2020·Oxidative Medicine and Cellular Longevity·Jianqiu PeiXi Chen
May 24, 2020·The Journal of Biological Chemistry·Soujanya VinayagamurthyShantanu Chowdhury
Jan 7, 2021·Clinical Science·Stephen J H DobbinNinian N Lang
Jan 16, 2021·Cellular and Molecular Life Sciences : CMLS·Emilie GuéritJean-Baptiste Demoulin
Aug 8, 2021·International Journal of Molecular Sciences·Jaslyn JohnsonSteven R Houser
May 25, 2021·Journal of Cardiovascular Pharmacology·Jia-Li YuanQun-Shan Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.