Signaling pathways that control rho kinase activity maintain the embryonic epicardial progenitor state.

The Journal of Biological Chemistry
Mykhaylo V ArtamonovAvril V Somlyo

Abstract

This study identifies signaling pathways that play key roles in the formation and maintenance of epicardial cells, a source of progenitors for coronary smooth muscle cells (SMCs). After epithelial to mesenchymal transition (EMT), mesenchymal cells invade the myocardium to form coronary SMCs. RhoA/Rho kinase activity is required for EMT and for differentiation into coronary SMCs, whereas cAMP activity is known to inhibit EMT in epithelial cells by an unknown mechanism. We use outgrowth of epicardial cells from E9.5 isolated mouse proepicardium (PE) explants, wild type and Epac1 null E12.5 mouse heart explants, adult rat epicardial cells, and immortalized mouse embryonic epicardial cells as model systems to identify signaling pathways that regulate RhoA activity to maintain the epicardial progenitor state. We demonstrate that RhoA activity is suppressed in the epicardial progenitor state, that the cAMP-dependent Rap1 GTP exchange factor (GEF), Epac, known to down-regulate RhoA activity through activation of Rap1 GTPase activity increased, that Rap1 activity increased, and that expression of the RhoA antagonistic Rnd proteins known to activate p190RhoGAP increased and associated with p190RhoGAP. Finally, EMT is associated with inc...Continue Reading

References

Apr 18, 1997·The Journal of Biological Chemistry·M C GongA P Somlyo
Oct 23, 1997·Developmental Dynamics : an Official Publication of the American Association of Anatomists·J M Pérez-PomaresR Muñoz-Chápuli
Oct 19, 2000·Methods in Enzymology·X D Ren, M A Schwartz
Feb 26, 2003·Circulation Research·Aya M WadaDavid M Bader
Mar 15, 2003·The Journal of Biological Chemistry·Kent L RossmanJohn Sondek
May 30, 2003·Molecular and Cellular Biology·Kirsi RientoAnne J Ridley
Jul 5, 2003·Current Biology : CB·Krister WennerbergSteen H Hansen
Jul 31, 2003·The Journal of Biological Chemistry·Holger RehmannJohannes L Bos
Oct 21, 2003·International Journal of Cancer. Journal International Du Cancer·Juan F SantibáñezJorge Martínez
Jul 13, 2004·Trends in Cell Biology·Andre Bernards, Jeffrey Settleman
Jul 16, 2004·Molecular and Cellular Biology·Catherine HoganYasuyuki Fujita
Jul 15, 2005·The Journal of Biological Chemistry·Tomohiro YamadaYoshimi Takai
Dec 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Esther MerkiPilar Ruiz-Lozano
Jan 25, 2006·Nature Methods·Jolanta SzulcPatrick Aebischer
Feb 14, 2006·Methods in Enzymology·Rafael García-MataKeith Burridge
Feb 24, 2006·Nature Reviews. Molecular Cell Biology·Pierre Chardin
Mar 4, 2006·The Journal of Biological Chemistry·Sarita K SastryKeith Burridge
Aug 10, 2006·American Journal of Physiology. Renal Physiology·Aihua ZhangTianxin Yang
Mar 24, 2007·Cellular and Molecular Life Sciences : CMLS·E M Winter, A C Gittenberger-de Groot
Dec 8, 2007·Journal of Cellular Physiology·Anna A BirukovaKonstantin G Birukov
Jan 24, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Anita F AustinJoey V Barnett
Feb 26, 2008·The Biochemical Journal·Ko MomotaniAvril V Somlyo
May 16, 2008·Nature·Chen-Leng CaiSylvia M Evans
Aug 30, 2008·Regenerative Medicine·Bin Zhou, William T Pu
Dec 20, 2008·The Journal of Biological Chemistry·Ronald L NepplAvril V Somlyo
Dec 24, 2008·The Journal of Biological Chemistry·Kazutaka MoriKozo Kaibuchi
Aug 21, 2009·American Journal of Physiology. Cell Physiology·Jeremy BregeonMalvyne Rolli-Derkinderen
Sep 3, 2009·The Biochemical Journal·James P MadiganAdrienne D Cox

❮ Previous
Next ❯

Citations

Dec 8, 2015·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Laura ArizaRamón Muñoz-Chápuli
Jun 25, 2016·Nature Reviews. Drug Discovery·Robert G GourdiePeter Kohl
Mar 21, 2017·Biochemical and Biophysical Research Communications·Song-Bai DengQiang She
Mar 15, 2018·Physiological Reviews·William G Robichaux, Xiaodong Cheng
Feb 16, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Suya WangAlexander R Moise
Apr 14, 2018·Journal of Cardiovascular Development and Disease·Jiayi TaoDiana Ramírez-Bergeron
Apr 16, 2021·Molecular Neurobiology·Bryce W DuncanPatricia F Maness

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

Cardiac Regeneration

Cardiac regeneration enables the repair of irreversibly damaged heart tissue using cutting-edge science, including stem cell and cell-free therapy. Discover the latest research on cardiac regeneration here.