Back to Search
Start Over
Targeting FSTL1 for Multiple Fibrotic and Systemic Autoimmune Diseases.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2021 Jan 06; Vol. 29 (1), pp. 347-364. Date of Electronic Publication: 2020 Sep 23. - Publication Year :
- 2021
-
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.<br /> (Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Autoimmune Diseases drug therapy
Autoimmune Diseases pathology
Disease Models, Animal
Drug Discovery
Fibrosis
Follistatin-Related Proteins antagonists & inhibitors
Follistatin-Related Proteins genetics
Gene Expression
Humans
Idiopathic Pulmonary Fibrosis drug therapy
Idiopathic Pulmonary Fibrosis pathology
Mice
Molecular Targeted Therapy
Transforming Growth Factor beta1 metabolism
Autoimmune Diseases etiology
Autoimmune Diseases metabolism
Biomarkers
Disease Susceptibility
Follistatin-Related Proteins metabolism
Idiopathic Pulmonary Fibrosis etiology
Idiopathic Pulmonary Fibrosis metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1525-0024
- Volume :
- 29
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 33007201
- Full Text :
- https://doi.org/10.1016/j.ymthe.2020.09.031