| Literature DB >> 33007201 |
Xiaohe Li1, Yinshan Fang1, Dingyuan Jiang2, Yingying Dong1, Yingying Liu1, Si Zhang1, Jiasen Guo1, Chao Qi1, Chenjing Zhao1, Fangxin Jiang1, Yueyue Jin1, Jing Geng2, Cheng Yang1, Hongkai Zhang1, Bin Wei3, Jiurong Liang4, Chen Wang2, Huaping Dai2, Honggang Zhou5, Dianhua Jiang6, Wen Ning7.
Abstract
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)-β1-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-β1 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.Entities:
Keywords: autoimmune diseases; follistatin-like 1; neutralizing antibodies; organ fibrosis; therapeutic strategy
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Year: 2020 PMID： 33007201 PMCID： PMC7791083 DOI： 10.1016/j.ymthe.2020.09.031
Source DB: PubMed Journal: Mol Ther ISSN： 1525-0016 Impact factor: 11.454