Role of Interleukin 34 in Pulmonary Vascular Remodeling Associated With Fibrosing Interstitial Lung Disease
8 affiliations
- 1Department of Cardiovascular Medicine Fukushima Medical University Fukushima Fukushima Japan
- 2Department of Community Cardiovascular Medicine Fukushima Medical University Fukushima Fukushima Japan
- 3Department of Hygiene and Preventive Medicine Fukushima Medical University Fukushima Fukushima Japan
- 4Department of Pulmonary Medicine Fukushima Medical University Fukushima Fukushima Japan
- 5Department of Diagnostic Pathology Fukushima Medical University Fukushima Fukushima Japan
- 6Department of Chest Surgery Fukushima Medical University Fukushima Fukushima Japan
- 7Department of Integrative Anatomy, Graduate School of Medical Sciences and Medical School Nagoya City University Nagoya Aichi Japan
- 8Department of Blood Transfusion and Transplantation Immunology Fukushima Medical University Fukushima Fukushima Japan
Abstract
Pulmonary hypertension with fibrosing interstitial lung disease is characterized by progressive pulmonary vascular remodeling and poor prognosis. Although inflammation and macrophage activation contribute to vascular remodeling, upstream mediators remain incompletely defined. Interleukin 34 (IL34), a ligand of colony‐stimulating factor‐1 receptor, regulates macrophage differentiation and recruitment. The objective is to elucidate the role of IL34 in pulmonary vascular remodeling associated with fibrosing interstitial lung disease. We investigated human lung samples, in vitro studies, using a murine model of pulmonary hypertension with fibrosing interstitial lung disease, and smooth muscle cell‐specific IL34‐deficient mice. IL34 expression was increased in the pulmonary arteries of patients with fibrosing interstitial lung disease with pulmonary vascular remodeling. IL34 was upregulated in pulmonary artery smooth muscle cells in a murine model of pulmonary hypertension with fibrosing interstitial lung disease, promoting osteopontin production in macrophages. Smooth muscle cell‐specific IL34 deficiency attenuated right ventricular systolic pressure, right ventricular hypertrophy, vascular remodeling, and perivascular macrophage accumulation in a murine model of pulmonary hypertension with fibrosing interstitial lung disease. Osteopontin from IL34‐induced macrophages promoted pulmonary artery smooth muscle cell proliferation. These findings identify smooth muscle cell‐derived IL34 as a contributor to pulmonary vascular remodeling associated with fibrosing interstitial lung disease.
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BibTeX
@article{yokokawa2026role,
title = {{Role of Interleukin 34 in Pulmonary Vascular Remodeling Associated With Fibrosing Interstitial Lung Disease}},
author = {Tetsuro Yokokawa and Shota Ueda and Kazuto Nishiura and Satoshi Okochi and Ryo Ogawara and Takatoyo Kiko and Shunsuke Miura and Tomofumi Misaka and Masayoshi Oikawa and Yusuke Masuishi and Takeyasu Kakamu and Yoshinori Tanino and Yoko Shibata and Yuko Hashimoto and Satoshi Muto and Hiroyuki Suzuki and Ken‐ichi Inoue and Kazuhiko Ikeda and Kazuhiko Nakazato and Takafumi Ishida and Yasuchika Takeishi},
journal = {Pulmonary circulation},
year = {2026},
month = oct,
doi = {10.1002/pul2.70446},
url = {https://europepmc.org/article/PMC/PMC13722307},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Role of Interleukin 34 in Pulmonary Vascular Remodeling Associated With Fibrosing Interstitial Lung Disease
AU - Tetsuro Yokokawa
AU - Shota Ueda
AU - Kazuto Nishiura
AU - Satoshi Okochi
AU - Ryo Ogawara
AU - Takatoyo Kiko
AU - Shunsuke Miura
AU - Tomofumi Misaka
AU - Masayoshi Oikawa
AU - Yusuke Masuishi
AU - Takeyasu Kakamu
AU - Yoshinori Tanino
AU - Yoko Shibata
AU - Yuko Hashimoto
AU - Satoshi Muto
AU - Hiroyuki Suzuki
AU - Ken‐ichi Inoue
AU - Kazuhiko Ikeda
AU - Kazuhiko Nakazato
AU - Takafumi Ishida
AU - Yasuchika Takeishi
PY - 2026
DA - 2026/10/01
JO - Pulmonary circulation
DO - 10.1002/pul2.70446
UR - https://europepmc.org/article/PMC/PMC13722307
AB - Pulmonary hypertension with fibrosing interstitial lung disease is characterized by progressive pulmonary vascular remodeling and poor prognosis. Although inflammation and macrophage activation contribute to vascular remodeling, upstream mediators remain incompletely defined. Interleukin 34 (IL34), a ligand of colony‐stimulating factor‐1 receptor, regulates macrophage differentiation and recruitment. The objective is to elucidate the role of IL34 in pulmonary vascular remodeling associated with fibrosing interstitial lung disease. We investigated human lung samples, in vitro studies, using a murine model of pulmonary hypertension with fibrosing interstitial lung disease, and smooth muscle cell‐specific IL34‐deficient mice. IL34 expression was increased in the pulmonary arteries of patients with fibrosing interstitial lung disease with pulmonary vascular remodeling. IL34 was upregulated in pulmonary artery smooth muscle cells in a murine model of pulmonary hypertension with fibrosing interstitial lung disease, promoting osteopontin production in macrophages. Smooth muscle cell‐specific IL34 deficiency attenuated right ventricular systolic pressure, right ventricular hypertrophy, vascular remodeling, and perivascular macrophage accumulation in a murine model of pulmonary hypertension with fibrosing interstitial lung disease. Osteopontin from IL34‐induced macrophages promoted pulmonary artery smooth muscle cell proliferation. These findings identify smooth muscle cell‐derived IL34 as a contributor to pulmonary vascular remodeling associated with fibrosing interstitial lung disease.
SN - 2045-8932
SN - 2045-8940
ER -