김효수 (서울대학교 의과대학, 서울대학교병원) | 한빛사논문 > 한빛사

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서울대학교 의과대학, 서울대학교병원

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Mol. Ther., Aug 28 2025, S1525-0016(25)00665-3 | https://doi.org/10.1016/j.ymthe.2025.08.035 Transcriptional intermediary factor 1 gamma prevents lung inflammation and fibrosis via alveolar type 2 cells, fibroblasts, and macrophages

Dodam Moon ³, Hyomin Park ³, Tae Yoon Kim ³, Areum Cha¹, Youngmin Kim ¹, Jaewon Lee ², Joong-Yub Kim ⁴, Samina Park ⁵, Sung-Hye Park ⁶, Jaemoon Koh⁶, Kyongman An ¹⁰, Nam-Joon Cho ^8,9, Taehoon Kim⁷, Eun Ju Lee ^1,2*, Hyo-Soo Kim ^1,2,3*

¹Interdisciplinary Program in Stem Cell Biology, Seoul National University of Medicine, Seoul 03080, Republic of Korea
²Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea
³Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Republic of Korea
⁴Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul 03080, Republic of Korea
⁵Department of Thoracic and Cardiovascular Surgery, Seoul 03080, Republic of Korea
⁶Department of Pathology, Seoul National University College of Medicine; Seoul 03080, Republic of Korea
⁷Department of Research and Development, LUCA AICell, Inc.; Anyang 14055, Republic of Korea
⁸School of Materials Science and Engineering, Nanyang Technological University; 50 Nanyang Avenue 639798, Singapore
⁹Centre for Cross Economy Global, 60 Nanyang Drive, School of Biological Sciences (SBS)-01s-50; Singapore 637551
¹⁰AI-Bio Convergence Research Institute, Department of Industrial AI Engineering, Graduate School of Management of Technology, Hoseo University, Asan City 31499, Republic of Korea

*These authors contributed equally as corresponding authors.
Correspondence should be addressed to Hyo-Soo Kim, MD, PhD
Corresponding author: Eun Ju Lee, PhD

Abstract

Transcriptional intermediary factor 1 gamma (TIF1γ) inhibits transforming growth factor-beta (TGFβ) signaling, the main pathway involved in fibrosis. We previously showed that TIF1γ regulated anti fibrotic processes in the liver. Herein, we aimed to evaluate the therapeutic potential of TIF1γ in pulmonary fibrosis (PF). TIF1γ inhibited the TGFβ-induced epithelial-mesenchymal transition in alveolar type 2 cells and activation of fibroblasts in vitro. In activated macrophages, TIF1γ reduced inflammatory cytokine secretion. In the in vivo PF mice model, TIF1γ significantly reduced fibrosis and improved lung function. In ex vivo fibrotic precision cut lung slices from mice and patients with PF, TIF1γ inhibited epithelial-mesenchymal transition of epithelial cells and activation of fibroblasts and reduced inflammatory cytokine secretion in macrophages. Conclusively, TIF1γ is a promising candidate of gene therapy for PF by modulating three cell types (alveolar type 2 cells, fibroblasts, and macrophages) involved in PF pathogenesis.

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