Abstract
Progressive tissue fibrosis is a cause of major morbidity and mortality. Pulmonary fibrosis is an epithelial-mesenchymal disorder in which TGF-β1 plays a central role in pathogenesis. Here we show that follistatin-like 1 (FSTL1) differentially regulates TGF-β and bone morphogenetic protein signaling, leading to epithelial injury and fibroblast activation. Haplodeletion of Fstl1 in mice or blockage of FSTL1 with a neutralizing antibody in mice reduced bleomycin-induced fibrosis in vivo. Fstl1 is induced in response to lung injury and promotes the accumulation of myofibroblasts and subsequent fibrosis. These data suggest that Fstl1 may serve as a novel therapeutic target for treatment of progressive lung fibrosis.
© 2015 Dong et al.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aged
-
Animals
-
Antibiotics, Antineoplastic / adverse effects
-
Antibodies, Monoclonal / pharmacology
-
Antibodies, Neutralizing / pharmacology
-
Bleomycin / adverse effects
-
Bone Morphogenetic Protein 4 / metabolism
-
Cell Communication
-
Cell Line
-
Disease Models, Animal
-
Female
-
Follistatin-Related Proteins / antagonists & inhibitors
-
Follistatin-Related Proteins / deficiency
-
Follistatin-Related Proteins / genetics*
-
Follistatin-Related Proteins / metabolism
-
Gene Expression
-
Humans
-
Inflammation / genetics
-
Inflammation / immunology
-
Inflammation / metabolism
-
Inflammation / pathology
-
Lung Injury / chemically induced
-
Lung Injury / genetics
-
Lung Injury / metabolism
-
Lung Injury / pathology
-
Male
-
Mesenchymal Stem Cells / metabolism
-
Mice
-
Mice, Knockout
-
Middle Aged
-
Myofibroblasts / immunology
-
Myofibroblasts / metabolism
-
Phenotype
-
Protein Binding
-
Pulmonary Fibrosis / chemically induced
-
Pulmonary Fibrosis / drug therapy
-
Pulmonary Fibrosis / genetics*
-
Pulmonary Fibrosis / metabolism
-
Respiratory Mucosa / immunology
-
Respiratory Mucosa / metabolism
-
Respiratory Mucosa / pathology
-
Signal Transduction
-
Smad Proteins / metabolism
-
Transforming Growth Factor beta1 / metabolism
Substances
-
Antibiotics, Antineoplastic
-
Antibodies, Monoclonal
-
Antibodies, Neutralizing
-
Bone Morphogenetic Protein 4
-
Follistatin-Related Proteins
-
Smad Proteins
-
Transforming Growth Factor beta1
-
Bleomycin
-
FSTL1 protein, human