单位：[1]State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, College of Pharmacy, Tianjin Key Laboratory of Protein Sciences, Nankai University, Tianjin300071, China[2]Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing 100029, China[3]Department of Surgery, Hospital ofBeijing Armed Police Corps, Beijing 100027, China[4]Department of Medicine and Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA90048, USA
Follistatin-like 1 (FSTL1) is a matricellular protein that is upregulated during development and disease, including idiopathic pulmonary fibrosis (IPF), keloid, and arthritis. The profibrotic and pro-inflammatory roles of FSTL1 have been intensively studied during the last several years, as well as in this report. We screened and identified epitope-specific monoclonal neutralizing antibodies (nAbs) to functionally block FSTL1. FSTL1 nAbs attenuated bleomycin-induced pulmonary and dermal fibrosis in vivo and transforming growth factor (TGF)-beta 1-induced dermal fibrosis ex vivo in human skin. In addition, FSTL1 nAbs significantly reduced existing lung fibrosis and skin fibrosis in experimental models. FSTL1 nAbs exerted their potent antifibrotic effects via reduced TGF-beta 1 responsiveness and subsequent myofibroblast activation and extracellular matrix production. We also observed that FSTL1 nAbs attenuated the severity of collagen-induced arthritis in mice, which was accompanied by reduced inflammatory responses in vitro. Our findings suggest that FSTL1 nAbs are a promising new therapeutic strategy for the treatment of multiple organ fibrosis and systemic autoimmune diseases.
基金：
National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China (NSFC) [31071241, 31471373, 31871460, 81430001]; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program" of China [2019ZX09201001-004-002]; Fundamental Research Funds for the Central Universities of Nankai University [63171410]; 111 Project of ChinaMinistry of Education, China - 111 Project [B08011]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P01 HL108793, R01 HL122068]
语种：
外文
被引次数：
WOS：
中科院(CAS)分区：
出版当年[2020]版：
大类|1 区医学
小类|1 区生物工程与应用微生物1 区遗传学1 区医学：研究与实验
最新[2025]版：
大类|1 区医学
小类|1 区生物工程与应用微生物1 区遗传学1 区医学：研究与实验
JCR分区：
出版当年[2019]版：
Q1MEDICINE, RESEARCH & EXPERIMENTALQ1BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ1GENETICS & HEREDITY
最新[2023]版：
Q1BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ1GENETICS & HEREDITYQ1MEDICINE, RESEARCH & EXPERIMENTAL
第一作者单位：[1]State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, College of Pharmacy, Tianjin Key Laboratory of Protein Sciences, Nankai University, Tianjin300071, China
通讯作者：
通讯机构：[1]State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, College of Pharmacy, Tianjin Key Laboratory of Protein Sciences, Nankai University, Tianjin300071, China[4]Department of Medicine and Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA90048, USA[*1]State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, College of Pharmacy, Tianjin Key Laboratory of Protein Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China[*2]Department of Medicine and Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.[*3]State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, College of Pharmacy, Tianjin Key Laboratory of Protein Sciences, Nankai University, 38 Tongyan Road, Tianjin 300350, China.
推荐引用方式(GB/T 7714)：
Li Xiaohe,Fang Yinshan,Jiang Dingyuan,et al.Targeting FSTL1 for Multiple Fibrotic and Systemic Autoimmune Diseases[J].MOLECULAR THERAPY.2021,29(1):347-364.doi:10.1016/j.ymthe.2020.09.031.
APA：
Li, Xiaohe,Fang, Yinshan,Jiang, Dingyuan,Dong, Yingying,Liu, Yingying...&Ning, Wen.(2021).Targeting FSTL1 for Multiple Fibrotic and Systemic Autoimmune Diseases.MOLECULAR THERAPY,29,(1)
MLA：
Li, Xiaohe,et al."Targeting FSTL1 for Multiple Fibrotic and Systemic Autoimmune Diseases".MOLECULAR THERAPY 29..1(2021):347-364
医学