Follistatin-like 3 mediates paracrine fibroblast activation by cardiomyocytes

Follistatins are extracellular inhibitors of the TGF-β family ligands including activin A, myostatin and bone morphogenetic proteins. Follistatin-like 3 (FSTL3) is a potent inhibitor of activin signalling and antagonises the cardioprotective role of activin A in the heart. FSTL3 expression is elevat...

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Bibliographic Details
Authors: Panse, Kalyani D, Felkin, Leanne E, Lopez-Olaneta, Marina, Gomez-Salinero, Jesus M., Villalba-Orero, Maria, Munoz, Lucia, Nakamura, Kazuto, Shimano, Masayuki, Walsh, Kenneth, Barton, Paul J R, Rosenthal, Nadia, Lara-Pezzi, Enrique
Format: article
Publication Date:2012
Country:España
Institution:Instituto de Salud Carlos III (ISCIII)
Repository:Repisalud
Language:English
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/7981
Online Access:http://hdl.handle.net/20.500.12105/7981
Access Level:Open access
Keyword:Animals
Cell Adhesion
Cell Proliferation
Cells, Cultured
Coculture Techniques
Collagen
Connective Tissue Growth Factor
Disease Models, Animal
Fibroblasts
Fibrosis
Follistatin-Related Proteins
Gene Expression Regulation
Heart Failure
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocytes, Cardiac
Proteins
Rats
Signal Transduction
Time Factors
Paracrine Communication
Description
Summary:Follistatins are extracellular inhibitors of the TGF-β family ligands including activin A, myostatin and bone morphogenetic proteins. Follistatin-like 3 (FSTL3) is a potent inhibitor of activin signalling and antagonises the cardioprotective role of activin A in the heart. FSTL3 expression is elevated in patients with heart failure and is upregulated in cardiomyocytes by hypertrophic stimuli, but its role in cardiac remodelling is largely unknown. Here, we show that the production of FSTL3 by cardiomyocytes contributes to the paracrine activation of cardiac fibroblasts, inducing changes in cell adhesion, promoting proliferation and increasing collagen production. We found that FSTL3 is necessary for this response and for the induction of cardiac fibrosis. However, full activation requires additional factors, and we identify connective tissue growth factor as a FSTL3 binding partner in this process. Together, our data unveil a novel mechanism of paracrine communication between cardiomyocytes and fibroblasts that may provide potential as a therapeutic target in heart remodelling.

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