title: Follistatin-like 1 protects against hypoxia-induced pulmonary hypertension in mice.
abstract: Pulmonary hypertension (PH) remains a life-limiting disease characterized by pulmonary vascular remodelling due to aberrant proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), thus leading to raised pulmonary arterial pressure and right ventricular hypertrophy. Secreted glycoprotein follistatin-like 1 (FSTL1) has been reported to ameliorate tissue remodelling in cardiovascular injuries. However, the role of FSTL1 in deranged pulmonary arteries remains elusive. We found that there were higher serum levels of FSTL1 in patients with PH related to chronic obstructive pulmonary diseases (COPD) and in mice model of hypoxia-induced PH (HPH). Haploinsufficiency of Fstl1 in mice contributed to an exacerbated HPH, as demonstrated by increased right ventricular systolic pressure, pulmonary arterial muscularization and right ventricular hypertrophy index. Conversely, FSTL1 administration attenuated HPH. In cultured human PASMCs, hypoxia-promoted cellular viability, DNA synthesis and migration were suppressed by exogenous FSTL1 but enhanced by small interfering RNA targeting FSTL1. Additionally, FSTL1 inhibited the proliferation and migration of PASMCs via extracellular regulated kinase (ERK) signal pathway. All these findings indicate that FSTL1 imposed a protective modulation on pulmonary vascular remodelling, thereby suggesting its role in the regulation of HPH.
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University, Beijing 100069, P.R. China.|Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University, Beijing 100069, P.R. China.|Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Wang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University, Beijing 100069, P.R. China.|Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Respiratory Department, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Jinna
authors.initials: J
authors.lastname: Li
authors.affiliation: Respiratory Department, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University, Beijing 100069, P.R. China.|Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University, Beijing 100069, P.R. China.|Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, Beijing 100029, P.R. China.
authors.forename: Yankun
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P.R. China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Respiratory Department, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.affiliation: Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Capital Medical University, Beijing 100069, P.R. China.|Department of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, Beijing 100029, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Ning
authors.affiliation: Department of Physiology and Pathophysiology, Capital Medical University, Beijing 100069, P.R. China.|Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D038702:Follistatin-Related Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D000860:Hypoxia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage
chemical_list: D038702:Follistatin-Related Proteins; C448720:Fstl1 protein, mouse; D034741:RNA, Small Interfering; C448799:FSTL1 protein, human