한빛사
>
한빛사논문
한빛사논문
- 조회175
Eur. Resp. J., Jan 09 2025, 2400615 | https://doi.org/10.1183/13993003.00615-2024
Inhibition of AXL ameliorates pulmonary fibrosis via attenuation of M2 macrophage polarization
Dong Ha Kim1,10 Kyungtaek Im1,10 In-Jeoung Baek2 Yun Jung Choi1 Hyeonjeong Lee1 Da-Som Kim3 Chae Won Lee3 JaeYi Jeong3 Kyosun Ban3 Sang-Yeob Kim4 Wonjun Ji5 Jae Cheol Lee6 Hyun-Yi Kim7 Yoonji Lee8 Yeongin Yang8 Miyong Yun9 Ho Cheol Kim5 Chang Min Choi5,6 Jin Kyung Rho3,4
1Asan Institute for Life Sciences, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
2Department of Cell and Genetic Engineering, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
3Department of Biochemistry and Molecular Biology, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
4Department of Convergence Medicine, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
5Department of Pulmonology and Critical Care Medicine, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
6Department of Oncology, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
7NGeneS Inc, Gyeonggi-do, South Korea
8Qurient Co., Ltd, Gyeonggi-do, South Korea
9Lab of Functional Aptamer, Department of Bioindustry and Bioresource Engineering, College of Life Sciences, Sejong University, Seoul, South Korea
10D. H. Kim and K.Im contributed equally to this work.
Corresponding authors: Ho Cheol Kim; Chang-Min Choi; Jin Kyung Rho
1Asan Institute for Life Sciences, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
2Department of Cell and Genetic Engineering, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
3Department of Biochemistry and Molecular Biology, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
4Department of Convergence Medicine, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
5Department of Pulmonology and Critical Care Medicine, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
6Department of Oncology, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
7NGeneS Inc, Gyeonggi-do, South Korea
8Qurient Co., Ltd, Gyeonggi-do, South Korea
9Lab of Functional Aptamer, Department of Bioindustry and Bioresource Engineering, College of Life Sciences, Sejong University, Seoul, South Korea
10D. H. Kim and K.Im contributed equally to this work.
Corresponding authors: Ho Cheol Kim; Chang-Min Choi; Jin Kyung Rho
Abstract
Although a relationship between the Gas6/AXL pathway and pulmonary fibrosis (PF) has been suggested, the precise mechanisms and clinical implications of the AXL pathway in idiopathic pulmonary fibrosis (IPF) are still unclear.
Constitutive and conditional AXL-knockout mice were generated and injected with bleomycin (BLM) to induce pulmonary fibrosis. The expression of AXL and macrophage subtypes in BLM-injected mice and patients with IPF was analysed using flow cytometry. The therapeutic effects of the AXL inhibitors were examined.
AXL-deficient mice were resistant to BLM-induced pulmonary fibrosis and had a lower degree of M2-like macrophage differentiation than wild-type mice. Interestingly, AXL expression in monocytes was enhanced according to the progression of BLM-induced pulmonary fibrosis (PF), and these results were especially prominent in Ly6Chigh monocytes. Gene silencing or inhibitor treatment with AXL inhibited the differentiation of M2-like macrophages during bone marrow-derived macrophage (BMDMs) differentiation. These results were confirmed through experiments using AXLfl/flLysMCre+ mice and systems with depletion and reconstitution of macrophages. In line with these results, patients with severe IPF had higher AXL expression in monocytes, high GAS6 levels, and an enhanced population of M2-like macrophages than those with mild IPF. Lastly, treatment with AXL inhibitors ameliorated BLM-induced PF and improved survival rate.
The AXL pathway in classical monocytes contributed to PF progression through the induction of M2-like macrophage differentiation. Therefore, targeting AXL may be a promising therapeutic option for PF.
논문정보
- Research article
- 2025년 01월 (BRIC 등록일 2025-01-10)
- 국내 연구진
- 의약학 > 면역의학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
