{"doi":"10.1073/pnas.1007293108","title":"Follistatin-like 1 (Fstl1) is a bone morphogenetic protein (BMP) 4 signaling antagonist in controlling mouse lung development","abstract":"<jats:p>\n                    Lung morphogenesis is a well orchestrated, tightly regulated process through several molecular pathways, including TGF-β/bone morphogenetic protein (BMP) signaling. Alteration of these signaling pathways leads to lung malformation. We investigated the role of Follistatin-like 1 (Fstl1), a secreted follistatin-module–containing glycoprotein, in lung development. Deletion of\n                    <jats:italic>Fstl1</jats:italic>\n                    in mice led to postnatal lethality as a result of respiratory failure. Analysis of the mutant phenotype showed that Fstl1 is essential for tracheal cartilage formation and alveolar maturation. Deletion of the\n                    <jats:italic>Fstl1</jats:italic>\n                    gene resulted in malformed tracheal rings manifested as discontinued rings and reduced ring number.\n                    <jats:italic>Fstl1</jats:italic>\n                    -deficient mice displayed septal hypercellularity and end-expiratory atelectasis, which were associated with impaired differentiation of distal alveolar epithelial cells and insufficient production of mature surfactant proteins. Mechanistically, Fstl1 interacted directly with BMP4, negatively regulated BMP4/Smad1/5/8 signaling, and inhibited BMP4-induced surfactant gene expression. Reducing BMP signaling activity by Noggin rescued pulmonary atelectasis of\n                    <jats:italic>Fstl1</jats:italic>\n                    -deficient mice. Therefore, we provide in vivo and in vitro evidence to demonstrate that Fstl1 modulates lung development and alveolar maturation, in part, through BMP4 signaling.\n                  </jats:p>","journal":"Proceedings of the National Academy of 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Ning","orcid":null,"position":14,"is_corresponding":false},{"id":189516,"name":"Yan Geng","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.393627546352361,"endowment":5.393627546352361,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21482757","pmcid":"PMC3084141","openalex_id":"https://openalex.org/W2042250615","authors":[],"funders":[],"total_grants":0,"fwci":6.7753,"citation_percentile":0.97044719,"influential_citations":10,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":8},{"year":2014,"count":11},{"year":2015,"count":16},{"year":2016,"count":15},{"year":2017,"count":27},{"year":2018,"count":15},{"year":2019,"count":15},{"year":2020,"count":24},{"year":2021,"count":20},{"year":2022,"count":20},{"year":2023,"count":13},{"year":2024,"count":9},{"year":2025,"count":11},{"year":2026,"count":5}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://europepmc.org/articles/pmc3084141?pdf=render","host_type":"GREEN"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1007293108","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1007293108","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21482757","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3084141","host_type":"repository"}],"fields_of_study":["Neonatal Respiratory Health Research","Congenital Diaphragmatic Hernia Studies","Medical Imaging and Pathology Studies","Biology","Medicine","Animals","Bone Morphogenetic Protein 4","Carrier Proteins","Cartilage","Cell Line, Tumor","Follistatin-Related Proteins","Gene Expression Regulation, Developmental","Humans","Mice","Mice, Knockout","Pulmonary Alveoli","Pulmonary Surfactants","Signal Transduction","Smad Proteins","Trachea","Noggin Protein"],"mesh_terms":["Noggin Protein","Animals","Carrier Proteins","Cartilage","Humans","Pulmonary Alveoli","Pulmonary Surfactants","Trachea","Signal Transduction","Mice, Knockout","Gene Expression Regulation, Developmental","Follistatin-Related Proteins","Cell Line, Tumor","Mice","Smad Proteins","Bone Morphogenetic Protein 4"],"keywords":["Follistatin","Noggin","Bone morphogenetic protein","Cell biology","Bone morphogenetic protein 4","Autocrine signalling","Signal transduction","Biology","BMPR2","Lung","Bone morphogenetic protein 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