期刊
MOLECULAR THERAPY
卷 29, 期 1, 页码 347-364出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2020.09.031
关键词
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资金
- 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 China [B08011]
- NIH [P01 HL108793, R01 HL122068]
The study showed that FSTL1 nAbs exerted potent antifibrotic effects by reducing TGF-β1 responsiveness, myofibroblast activation, and extracellular matrix production. These antibodies also reduced the severity of collagen-induced arthritis in mice and inflammatory responses in vitro.
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.
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