Format

Send to

Choose Destination
EMBO Mol Med. 2016 Aug 1;8(8):949-66. doi: 10.15252/emmm.201506151. Print 2016 Aug.

Follistatin-like 1 promotes cardiac fibroblast activation and protects the heart from rupture.

Author information

1
Department of Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
2
Department of Anatomy, Embryology and Physiology, Academic Medical Center, Amsterdam, The Netherlands.
3
Molecular Cardiovascular Medicine, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
4
Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
5
Department of Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA kxwalsh@bu.edu.

Abstract

Follistatin-like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type-specific regulation of Fstl1 and its function in a murine model of MI Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area compared to cardiac myocytes. The conditional ablation of Fstl1 in S100a4-expressing fibroblast lineage cells (Fstl1-cfKO mice) led to a reduction in injury-induced Fstl1 expression and increased mortality due to cardiac rupture during the acute phase. Cardiac rupture was associated with a diminished number of myofibroblasts and decreased expression of extracellular matrix proteins. The infarcts of Fstl1-cfKO mice displayed weaker birefringence, indicative of thin and loosely packed collagen. Mechanistically, the migratory and proliferative capabilities of cardiac fibroblasts were attenuated by endogenous Fstl1 ablation. The activation of cardiac fibroblasts by Fstl1 was mediated by ERK1/2 but not Smad2/3 signaling. This study reveals that Fstl1 is essential for the acute repair of the infarcted myocardium and that stimulation of early fibroblast activation is a novel function of Fstl1.

KEYWORDS:

cardiokine; fibrosis; infarct healing; myocardial infarction

PMID:
27234440
PMCID:
PMC4967946
DOI:
10.15252/emmm.201506151
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center