Scientific reports, 2018-01, Vol.8 (1), p.342-15, Article 342
2018
Details
- Autor(en) / Beteiligte
- Titel
- A model of human lung fibrogenesis for the assessment of anti-fibrotic strategies in idiopathic pulmonary fibrosis
- Ist Teil von
- Scientific reports, 2018-01, Vol.8 (1), p.342-15, Article 342
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options. K 3.1 ion channels play a critical role in TGFβ1-dependent pro-fibrotic responses in human lung myofibroblasts. We aimed to develop a human lung parenchymal model of fibrogenesis and test the efficacy of the selective K 3.1 blocker senicapoc. 2 mm pieces of human lung parenchyma were cultured for 7 days in DMEM ± TGFβ1 (10 ng/ml) and pro-fibrotic pathways examined by RT-PCR, immunohistochemistry and collagen secretion. Following 7 days of culture with TGFβ1, 41 IPF- and fibrosis-associated genes were significantly upregulated. Immunohistochemical staining demonstrated increased expression of ECM proteins and fibroblast-specific protein after TGFβ1-stimulation. Collagen secretion was significantly increased following TGFβ1-stimulation. These pro-fibrotic responses were attenuated by senicapoc, but not by dexamethasone. This 7 day ex vivo model of human lung fibrogenesis recapitulates pro-fibrotic events evident in IPF and is sensitive to K 3.1 channel inhibition. By maintaining the complex cell-cell and cell-matrix interactions of human tissue, and removing cross-species heterogeneity, this model may better predict drug efficacy in clinical trials and accelerate drug development in IPF. K 3.1 channels are a promising target for the treatment of IPF.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-017-18555-9Titel-ID: cdi_doaj_primary_oai_doaj_org_article_46976a4f4c0e44a38515a896ef024507
- Format
- –
- Schlagworte
- Cell culture, Cell Survival - genetics, Cells, Cultured, Clinical trials, Collagen, Collagen - metabolism, Dexamethasone, Dexamethasone - pharmacology, Drug development, Energy Metabolism, Extracellular matrix, Fibroblasts - drug effects, Fibroblasts - metabolism, Fibroblasts - pathology, Fibrosis, Gene Expression Profiling, Humans, Idiopathic Pulmonary Fibrosis - drug therapy, Idiopathic Pulmonary Fibrosis - etiology, Idiopathic Pulmonary Fibrosis - metabolism, Idiopathic Pulmonary Fibrosis - pathology, Immunohistochemistry, Intermediate-Conductance Calcium-Activated Potassium Channels - metabolism, Ion channels, Lung diseases, Models, Biological, Parenchyma, Polymerase chain reaction, Pulmonary fibrosis, Tissue Culture Techniques, Transcriptome, Transforming Growth Factor beta1 - metabolism, Transforming growth factor-b1