Epigenetic Dysregulation of the <scp>NKX2</scp> ‐1/ <scp>SPDEF</scp> Axis Drives Persistent Goblet Cell Differentiation and Epithelial Barrier Dysfunction in Chronic Obstructive Pulmonary Disease
Epigenetic mechanisms maintain persistent alterations in airway epithelial differentiation after smoking cessation, leading to mucus-producing cell hyperplasia through dysregulation of the NKX2-1/SPDEF axis. This hyperplasia correlates with reduced junction-associated molecule expression and subsequent barrier dysfunction. Therapeutic strategies targeting epithelial barrier restoration and/or normalisation of epigenetic dysregulation may benefit patients with COPD, even after smoking cessation.
Authors
- Shingo Usuki (ORCID: https://orcid.org/0000-0002-9959-3322)
- Ayaka Shiota
- Mizuho A. Kido (ORCID: https://orcid.org/0000-0002-9348-0706)
- Shigesato Inoue (ORCID: https://orcid.org/0000-0001-7423-0659)
- Etsuro Ogata (ORCID: https://orcid.org/0000-0002-0046-5575)
- Koichiro Matsumoto (ORCID: https://orcid.org/0000-0003-2242-8131)
- Tatsuya Katsuno (ORCID: https://orcid.org/0000-0002-0395-4382)
- Yumiko Ishii (ORCID: https://orcid.org/0000-0002-7438-3695)
- Takeshi Sawada (ORCID: https://orcid.org/0000-0001-7000-2296)
- T Koga
- Akihiro Jo
- Sachiko Tsukita
- Isamu Okamoto
- Keiko Kan‐o
- Tomohiro Ogawa
- Kei‐ichiro Yasunaga
- Mitsuyoshi Nakao
Institutions
- Kyushu University (JP)
- Kumamoto Health Science University (JP)
- Saga University (JP)
- Kyoto University (JP)
- Ube Frontier University (JP)
- Fukuoka Hospital (JP)
- Omuta hospital (JP)
- Tokyo Women's Medical University (JP)
- Fukuoka Dental College (JP)
- Teikyo University (JP)
- Kumamoto University (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- Respirology
- Published
- 2026-01-20
- DOI
- https://doi.org/10.1002/resp.70201
- Citations
- 1
- Primary Topic
- Neonatal Respiratory Health Research
- Type
- article
- Field-Weighted Citation Impact
- 36.44