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A novel peptide binding to the C-terminal domain of connective tissue growth factor for the treatment of bleomycin-induced pulmonary fibrosis
- Source :
- International Journal of Biological Macromolecules. 156:1464-1473
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Using phage display technology, 810A was developed as a novel peptide, which binds to the C-terminal domain of connective tissue growth factor (CTGF). The present study investigated whether this peptide could neutralize CTGF and block its biological activity as a specific strategy to treat pulmonary fibrosis in vitro and in vivo. Human bronchial epithelial (16HBE) cells were treated with CTGF to evaluate the anti-CTGF capability of 810A using MTT testing, cell migration assays, and Western blotting. The action of 810A in mouse models of bleomycin (BLM)-induced pulmonary fibrosis was evaluated according to leukocyte counts in bronchoalveolar lavage fluid (BALF), hydroxyproline content, and pathological analysis. Treatment with 810A resulted in inhibition of cell proliferation, migration, and increases in transforming growth factor-beta (TGF-β) and α-Smooth muscle actin (α-SMA) caused by CTGF treatment in vitro. In vivo, 810A significantly alleviated fibrosis in the pulmonary index. Inflammation was inhibited, as inferred by the reduced number of leukocytes in BALF. Pathophysiological analysis indicated that hydroxyproline content, alveolar enlargement, interstitial inflammatory infiltration, and collagen deposition were reduced. Collectively, these data suggest that 810A may potentially be a CTGF-specific, small-molecule antagonist, providing a new method for prevention and treatment of pulmonary fibrosis.
- Subjects :
- Pulmonary Fibrosis
medicine.medical_treatment
Connective tissue
Peptide binding
02 engineering and technology
Bleomycin
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Protein Domains
Peptide Library
Structural Biology
In vivo
Fibrosis
Pulmonary fibrosis
medicine
Humans
Molecular Biology
030304 developmental biology
0303 health sciences
integumentary system
Growth factor
Connective Tissue Growth Factor
General Medicine
021001 nanoscience & nanotechnology
medicine.disease
Molecular biology
CTGF
medicine.anatomical_structure
chemistry
Peptides
0210 nano-technology
Protein Binding
Subjects
Details
- ISSN :
- 01418130
- Volume :
- 156
- Database :
- OpenAIRE
- Journal :
- International Journal of Biological Macromolecules
- Accession number :
- edsair.doi.dedup.....5fe7967236e49c43300b184829e799d8