한빛사논문
- 조회629
Soo Yeon Lee1,9, Soo-Yeon Park1,9, Seung-Hyun Lee1, Hyunsik Kim1, Jae-Hwan Kwon1, Jung-Yoon Yoo2, Kyunggon Kim3, Moo Suk Park4, Chun Geun Lee5,6, Jack A. Elias5, Myung Hyun Sohn7, Hyo Sup Shim8,* and Ho-Geun Yoon1,*
1Department of Biochemistry and Molecular Biology, Severance Medical Research Institute, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Korea.
2Department of Biomedical Laboratory Science, Yonsei University Mirae Campus, Wonju, South Korea.
3Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea.
5Molecular Microbiology and Immunology, Brown University, Providence, RI, USA.
6Department of Internal Medicine, Hanyang University, Seoul 04763, Korea.
7Department of Pediatrics and Institute of Allergy, Severance Medical Research Institute, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Korea.
8Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Korea.
9These authors contributed equally: Soo Yeon Lee, Soo-Yeon Park
*Corresponding author: correspondence to Hyo Sup Shim or Ho-Geun Yoon
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal, fibrotic, interstitial lung disease of unknown cause. Despite extensive studies, the underlying mechanisms of IPF development remain unknown. Here, we found that p300 was upregulated in multiple epithelial cells in lung samples from patients with IPF and mouse models of lung fibrosis. Lung fibrosis was significantly diminished by the alveolar type II (ATII) cell–specific deletion of the p300 gene. Moreover, we found that ubiquitin C-terminal hydrolase L3 (UCHL3)-mediated deubiquitination of p300 led to the transcriptional activation of the chemokines Ccl2, Ccl7, and Ccl12 through the cooperative action of p300 and C/EBPβ, which consequently promoted M2 macrophage polarization. Selective blockade of p300 activity in ATII cells resulted in the reprogramming of M2 macrophages into antifibrotic macrophages. These findings demonstrate a pivotal role for p300 in the development of lung fibrosis and suggest that p300 could serve as a promising target for IPF treatment.
논문정보
- Research article
- 2023년 08월 (BRIC 등록일 2023-08-02)
- 국내(교신)+국외 연구진
- 의약학 > 분자세포의학
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