1. Transcriptomic changes involved in the dedifferentiation of myofibroblasts derived from the lung of a patient with idiopathic pulmonary fibrosis
- Author
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Jun Ikari, Keita Ugai, Shuichi Matsuda, Akiyoshi Fukamizu, Hideki Mikami, Yoshitoshi Kasuya, Koichiro Tatsumi, Masahiko Hatano, Kenichi Suzuki, Jun-Dal Kim, and Kento Yoshioka
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Cell ,microRNA array ,Gene Expression ,Biochemistry ,Extracellular matrix ,Transcriptome ,03 medical and health sciences ,Idiopathic pulmonary fibrosis ,0302 clinical medicine ,transcriptome analysis ,Genetics ,medicine ,Humans ,Myofibroblasts ,Molecular Biology ,Lung ,Cells, Cultured ,Oncogene ,business.industry ,dedifferentiation ,Cell Differentiation ,Articles ,Azepines ,Middle Aged ,Triazoles ,respiratory system ,medicine.disease ,idiopathic pulmonary fibrosis ,Molecular medicine ,myofibroblast ,Actins ,Fibronectins ,respiratory tract diseases ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,business ,Myofibroblast - Abstract
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown etiology. Under pathological conditions in lungs with IPF, myofibroblasts serve a key role in fibrogenesis via the accumulation of an excessive amount of extracellular matrix. To develop effective therapeutic interventions against IPF, studies have recently focused on how to dedifferentiate established myofibroblasts. The present study revealed that JQ1, an inhibitor of bromodomain and extra‑terminal proteins, markedly suppressed the expression levels of α‑smooth muscle actin and ED‑A‑fibronectin in myofibroblasts prepared from the lung of a patient with end‑stage IPF. Furthermore, these findings were supported by transcriptome analysis using RNA sequencing, in which differentially expressed genes (DEGs) downregulated by JQ1 treatment were significantly enriched in the fibrosis‑related signaling pathway. On the other hand, the upregulated DEGs in response to JQ1 treatment were significantly enriched in glutathione metabolism, which may affect the cell status of fibroblast/myofibroblast. To the best of our knowledge, this was the first study to comprehensively analyze transcriptome profiles associated with dedifferentiation of IPF myofibroblasts.
- Published
- 2020