Blocking follistatin-like 1 attenuates bleomycin-induced pulmonary fibrosis in mice.
Bottom Line: 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.These data suggest that Fstl1 may serve as a novel therapeutic target for treatment of progressive lung fibrosis.
Affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China Cam-Su Genomic Resource Center, Soochow University, Suzhou 215123, China.Show MeSH
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Mentions: The accumulation of fibroblasts with an activated phenotype (named as myofibroblasts) in the fibrotic foci characterizes progressive pulmonary fibrosis (Scotton and Chambers, 2007; Phan, 2012). To examine whether the attenuated fibrotic phenotype in Fstl1+/− mice is associated with the changed accumulation of myofibroblasts, we performed immunohistochemistry on lung sections with anti–α-SMA antibodies, a marker for newly appearing myofibroblasts. As shown in Fig. 4 A, bleomycin-increased myofibroblast accumulation was apparent in WT mice, but not in Fstl1+/− mice. Consistently, qRT-PCR and immunoblotting analyses of lung tissues showed that bleomycin-induced expression of α-SMA in WT mice was significantly decreased in Fstl1+/− mice (Fig. 4, B and C). Meanwhile, we observed that the mRNA level of Fsp-1, a marker for fibroblasts, was lower in Fstl1+/− mice than that in WT (Fig. 4 D). These data suggest that Fstl1 deficiency is protective against fibrogenesis, possibly via limiting the bleomycin-induced accumulation of myofibroblasts.
Affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China Cam-Su Genomic Resource Center, Soochow University, Suzhou 215123, China.