A-kinase anchoring protein-Lbc promotes pro-fibrotic signaling in cardiac fibroblasts

Détails

ID Serval
serval:BIB_5EBB6D0C78D7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A-kinase anchoring protein-Lbc promotes pro-fibrotic signaling in cardiac fibroblasts
Périodique
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Auteur(s)
Cavin Sabrina, Maric Darko, Diviani Dario
ISSN
0167-4889
ISSN-L
1879-2596
Statut éditorial
Publié
Date de publication
02/2014
Peer-reviewed
Oui
Volume
1843
Numéro
2
Pages
335-345
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
In response to stress or injury the heart undergoes an adverse remodeling process associated with cardiomyocyte hypertrophy and fibrosis. Transformation of cardiac fibroblasts to myofibroblasts is a crucial event initiating the fibrotic process. Cardiac myofibroblasts invade the myocardium and secrete excess amounts of extracellular matrix proteins, which cause myocardial stiffening, cardiac dysfunctions and progression to heart failure. While several studies indicate that the small GTPase RhoA can promote profibrotic responses, the exchange factors that modulate its activity in cardiac fibroblasts are yet to be identified. In the present study, we show that AKAP-Lbc, an A-kinase anchoring protein (AKAP) with an intrinsic Rho-specific guanine nucleotide exchange factor (GEF) activity, is critical for activating RhoA and transducing profibrotic signals downstream of type I angiotensin II receptors (AT1Rs) in cardiac fibroblasts. In particular, our results indicate that suppression of AKAP-Lbc expression by infecting adult rat ventricular fibroblasts with lentiviruses encoding AKAP-Lbc specific short hairpin (sh) RNAs strongly reduces the ability of angiotensin II to promote RhoA activation, differentiation of cardiac fibroblasts to myofibroblasts, collagen deposition as well as myofibroblast migration. Interestingly, AT1Rs promote AKAP-Lbc activation via a pathway that requires the α subunit of the heterotrimeric G protein G12. These findings identify AKAP-Lbc as a key Rho-guanine nucleotide exchange factor modulating profibrotic responses in cardiac fibroblasts.
Mots-clé
Cell Biology, Molecular Biology
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/03/2014 19:33
Dernière modification de la notice
20/08/2019 14:16
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