title: 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-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.
authors.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.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Geng
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China Respiratory Department, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yinshan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
authors.forename: Jiurong
authors.initials: J
authors.lastname: Liang
authors.affiliation: Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
authors.forename: Huaping
authors.initials: H
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xinqi
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Noble
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048 ningwen108@nankai.edu.cn dianhua.jiang@cshs.org.
authors.forename: Dianhua
authors.initials: D
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China ningwen108@nankai.edu.cn dianhua.jiang@cshs.org.
authors.forename: Wen
authors.initials: W
authors.lastname: Ning
mesh_terms: D000368:Aged; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001761:Bleomycin / Q000009:adverse effects; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002450:Cell Communication; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D038702:Follistatin-Related Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D058628:Myofibroblasts / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D055415:Bone Morphogenetic Protein 4; D038702:Follistatin-Related Proteins; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; C448799:FSTL1 protein, human