Transcriptomic changes involved in the dedifferentiation of myofibroblasts derived from the lung of a patient with idiopathic pulmonary fibrosis

Suzuki,Kenichi; Suzuki,Kenichi; Suzuki,Kenichi; Kim,Jun‑Dal; Kim,Jun‑Dal; Kim,Jun‑Dal; Ugai,Keita; Ugai,Keita; Ugai,Keita; Matsuda,Shuichi; Matsuda,Shuichi; Matsuda,Shuichi; Mikami,Hideki; Mikami,Hideki; Mikami,Hideki; Yoshioka,Kento; Yoshioka,Kento; Yoshioka,Kento; Ikari,Jun; Ikari,Jun; Ikari,Jun; Hatano,Masahiko; Hatano,Masahiko; Hatano,Masahiko; Fukamizu,Akiyoshi; Fukamizu,Akiyoshi; Fukamizu,Akiyoshi; Tatsumi,Koichiro; Tatsumi,Koichiro; Tatsumi,Koichiro; Kasuya,Yoshitoshi; Kasuya,Yoshitoshi; Kasuya,Yoshitoshi

doi:10.3892/mmr.2020.11218

Transcriptomic changes involved in the dedifferentiation of myofibroblasts derived from the lung of a patient with idiopathic pulmonary fibrosis

Authors:
- Kenichi Suzuki
- Jun‑Dal Kim
- Keita Ugai
- Shuichi Matsuda
- Hideki Mikami
- Kento Yoshioka
- Jun Ikari
- Masahiko Hatano
- Akiyoshi Fukamizu
- Koichiro Tatsumi
- Yoshitoshi Kasuya
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Affiliations: Department of Biomedical Science, Graduate School of Medicine, Chiba University, Chuo‑ku, Chiba 260‑8670, Japan, Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki 305‑8577, Japan, Department of Respirology, Graduate School of Medicine, Chiba University, Chuo‑ku, Chiba 260‑8670, Japan
Published online on: June 10, 2020 https://doi.org/10.3892/mmr.2020.11218
Pages: 1518-1526
Copyright: © Suzuki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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