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Nagilactone D ameliorates experimental pulmonary fibrosis in vitro and in vivo via modulating TGF-β/Smad signaling pathway
- Source :
- Toxicology and Applied Pharmacology. 389:114882
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Pulmonary fibrosis is a prototypic chronic progressive lung disease with high morbidity and mortality worldwide. Novel effective therapeutic agents are urgently needed owing to the limited treatment options in clinic. Herein, nagilactone D (NLD), a natural dinorditerpenoid obtained from Podocarpus nagi, was found to suppress transforming growth factor-β1 (TGF-β1)-mediated fibrotic process in vitro and bleomycin (BLM)-induced pulmonary fibrosis in vivo. NLD attenuated TGF-β1-induced expression of fibrotic markers including type I and III collagen, fibronectin, α-SMA, and CTGF in human pulmonary fibroblasts (WI-38 VA-13 and HLF-1 cells). Mechanism study indicated that NLD suppressed TGF-β1-induced up-regulation of TβR I, and Smad2 phosphorylation, nuclear translocation, and transcriptional activation. Moreover, NLD ameliorated BLM-induced histopathological abnormalities in the lungs of experimental fibrotic mice, suppressed synthesis of relative fibrotic markers and fibroblast-to-myofibroblast transition, as well as BLM-induced up-regulation of TβR I expression and Smad signaling in mouse lungs. These data collectively support NLD to be a potential therapeutic agent for pulmonary fibrosis.
- Subjects :
- 0301 basic medicine
Pulmonary Fibrosis
Receptor, Transforming Growth Factor-beta Type I
Smad2 Protein
SMAD
Toxicology
Bleomycin
Transforming Growth Factor beta1
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
In vivo
Pulmonary fibrosis
Animals
Humans
Medicine
Myofibroblasts
Lung
Cells, Cultured
Pharmacology
Transition (genetics)
biology
Terpenes
business.industry
Fibroblasts
medicine.disease
In vitro
Mice, Inbred C57BL
CTGF
Fibronectin
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Cancer research
biology.protein
Female
Diterpenes
business
Biomarkers
Signal Transduction
Subjects
Details
- ISSN :
- 0041008X
- Volume :
- 389
- Database :
- OpenAIRE
- Journal :
- Toxicology and Applied Pharmacology
- Accession number :
- edsair.doi.dedup.....77233c13a1d7f968a54f14cd3246a8c6