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
Related in: MedlinePlus
License 1 - License 2
Mentions: Persistent inflammation often drives fibrotic progression in the bleomycin injury model, although the contribution of inflammation to fibrogenesis is controversial (Wynn, 2008). Previous studies have implicated a role of FSTL1 in inflammatory response in rheumatoid arthritis (Clutter et al., 2009) and in heart allograft rejection (Le Luduec et al., 2008). We analyzed the inflammatory response of Fstl1+/− mice 7 d after bleomycin treatment. Notably, compared with WT mice, the increase of inflammatory cells was comparable in Fstl1+/− mice (Fig. 3 A). Consistently, FACS analysis showed no major differences in immune cell subset infiltration, such as CD4+, CD8+, NKT, NK, and B cells, as well as alveolar and interstitial macrophages and neutrophils, in lung tissues between the mouse strains (Fig. 3 B). A Th1/Th2 imbalance has been suggested to play a role in fibrogenesis (Wynn, 2008). We measured cytokines IFN-γ (Th1), IL-13 (Th2), IL-6, IL-1β, IL-17A, and TNF, whose dysregulation has been reported in lung tissue of IPF patients (Agostini and Gurrieri, 2006; Wynn, 2011) and in animal models (Saito et al., 2008; Wynn, 2008). As shown in Fig. 3 C, similar concentrations of cytokines were measured by ELISA in the bronchoalveolar lavage (BAL) fluid (BALF) and homogenized lung tissue from Fstl1+/− and WT littermates. These data suggest that deletion of Fstl1 attenuates bleomycin-induced lung fibrosis without affecting the inflammatory response in response to lung injury.
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.