Involvement of lncRNA MIR205HG in idiopathic pulmonary fibrosis and IL-33 regulation via Alu elements
Idiopathic pulmonary fibrosis (IPF) causes remodeling of the distal lung. Pulmonary remodeling is histologically characterized by fibrosis, as well as appearance of basal cells; however, the involvement of basal cells in IPF remains unclear. Here, we focus on the long noncoding RNA MIR205HG, which is highly expressed in basal cells, using RNA sequencing. Through RNA sequencing of genetic manipulations using primary cells and organoids, we discovered that MIR205HG regulates IL-33 expression. Mechanistically, the AluJb element of MIR205HG plays a key role in IL-33 expression. Additionally, we identified a small molecule that targets the AluJb element, leading to decreased IL-33 expression. IL-33 is known to induce type 2 innate lymphoid cells (ILC2s), and we observed that MIR205HG expression was positively correlated with the number of ILC2s in patients with IPF. Collectively, these findings provide insights into the mechanisms by which basal cells contribute to IPF and suggest potential therapeutic targets.
Authors
- Ayako Sugai
- Daisuke Okuzaki (ORCID: https://orcid.org/0000-0002-4552-783X)
- Yasue Harada (ORCID: https://orcid.org/0000-0001-7146-0387)
- Kazuhiko Nakatani (ORCID: https://orcid.org/0000-0002-1705-5265)
- Hideki Nagata (ORCID: https://orcid.org/0000-0002-6690-0525)
- Michiaki Hamada (ORCID: https://orcid.org/0000-0001-9466-1034)
- Zhaozu Feng
- Tsuyoshi Takashima (ORCID: https://orcid.org/0000-0003-1362-3883)
- Chao Zeng (ORCID: https://orcid.org/0000-0002-6130-2438)
- Gota Kawai (ORCID: https://orcid.org/0000-0003-1480-2840)
- Rika Ichijo
- Tetsuro Hirose (ORCID: https://orcid.org/0000-0003-1068-5464)
- Satoshi Nojima (ORCID: https://orcid.org/0000-0002-5124-0026)
- Eitaro Murakami
- Takahiro Matsui (ORCID: https://orcid.org/0000-0002-6753-1688)
- Eiichi Morii (ORCID: https://orcid.org/0000-0001-8490-3650)
- Yasushi Shintani (ORCID: https://orcid.org/0000-0002-2540-5288)
- Masaharu Kohara (ORCID: https://orcid.org/0009-0006-7636-5833)
- Naoko Fujiwara (ORCID: https://orcid.org/0000-0003-2366-9076)
Institutions
- Waseda University (JP)
- Ube Frontier University (JP)
- ID Genomics (United States) (US)
- Suntory Foundation for Life Sciences (JP)
- National Institute of Advanced Industrial Science and Technology (JP)
- Chiba Institute of Technology (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- JCI Insight
- Published
- 2025-03-09
- DOI
- https://doi.org/10.1172/jci.insight.187172
- Citations
- 8
- Primary Topic
- IL-33, ST2, and ILC Pathways
- Type
- article
- Field-Weighted Citation Impact
- 6.38
Funders
- Japan Agency for Medical Research and Development
- Japan Society for the Promotion of Science