Blocking follistatin-like 1 attenuates bleomycin-induced pulmonary fibrosis in mice

Abstract

Progressive tissue fibrosis is a cause of major morbidity and mortality. Pulmonary fibrosis is an epithelial-mesenchymal disorder in which TGF-1 plays a central role in pathogenesis. Here we show that follistatin-like 1 (FSTL1) differentially regulates TGF- 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.

Anlotinib attenuated bleomycin-induced pulmonary fibrosis via the TGF-β1 signalling pathway

“…The right lung tissues of the mice in bleomycin‐induced pulmonary fibrosis model were isolated for determining the Hyp levels according to a modified method described by Dong Y et al …”

Structural and functional study of FK domain of Fstl1

“…Fstl1 has been implicated in several human diseases. Findings on Fstl1 in cardiovascular disease, cancer, arthritis, lung fibrosis, and obesity emphasize its potential as both biomarkers and targets for the management of the disease process. Although the functions and mechanisms of Fstl1 have not been completely understood, a growing body of literatures have identified the critical roles of Fstl1 in the regulation of cell survival, proliferation, differentiation, migration, as well as inflammation, and immune modulation .…”

“…Although the functions and mechanisms of Fstl1 have not been completely understood, a growing body of literatures have identified the critical roles of Fstl1 in the regulation of cell survival, proliferation, differentiation, migration, as well as inflammation, and immune modulation . Fstl1 is first discovered as a TGF‐β1‐induced protein, and has also been shown to function largely through regulating TGF‐β/BMP signaling, although, in various disease models, different signaling pathways, like activation of AKT, AMPK, or ERK–MAPK, are linked to Fstl1 …”

Follistatin‐like protein 1 modulates IL‐17 signaling via IL‐17RC regulation in stromal cells

“…FSTL‐1 has been identified in both secreted and intracellular compartments, suggesting differential cell trafficking regulation. Highly expressed in mammalian cells of mesenchymal lineage, several studies have implicated FSTL‐1 with functions in a myriad of settings, including embryonic development, cardiac and lung dysfunction and repair, as well as tumorigenesis and metastasis and inflammation 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 . In vivo modeling has been limited as FSTL‐1 germline knockout (KO) mice display a perinatal lethal phenotype associated with multiple lung, skeletal and urogenital defects.…”

“…In vivo modeling has been limited as FSTL‐1 germline knockout (KO) mice display a perinatal lethal phenotype associated with multiple lung, skeletal and urogenital defects. However, murine models have employed neutralizing antibodies, small‐interfering RNA, adenoviral‐gene transfer, partial gene disruption (FSTL‐1 hypomorphs) and FSTL‐1 transgenic models to begin characterizing in vivo functions of FSTL‐1 2 , 3 , 5 , 6 , 8 , 10 , 11 …”