| 게재년월 |
2022/04 |
| 논문제목 |
A Novel Regulatory Role of Activated Leukocyte Cell-Adhesion Molecule in the Pathogenesis of Pulmonary Fibrosis
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| 참여교수 |
손명현
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| 학술지명 |
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY |
| 초록 |
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by fibroproliferative matrix molecule accumulation, collagen deposition, and apoptosis. Activated leukocyte cell-adhesion molecule (ALCAM; CD166) is a cell-adhesion molecule that has been implicated in adhesive and migratory attribution, including leukocyte homing and trafficking and cancer metastasis. We investigated the role of ALCAM on pulmonary fibrosis development in murine models. Thus, a bleomycin-induced pulmonary fibrosis model was established with wild-type and ALCAM-/- mice. Pulmonary fibrosis was also induced in transforming growth factor-β1 (TGF-β1)-transgenic mice that conditionally overexpress TGF-β1 upon doxycycline administration. In both models, observed reduced ALCAM levels in lung tissue and BAL fluid in pulmonary fibrosis-induced wild-type mice compared with control mice. We also observed reduced ALCAM expression in the lung tissue of patients with pulmonary fibrosis compared with normal lung tissue. ALCAM-/- mice showed an exacerbated lung fibrosis response compared with wild-type mice, and this was accompanied by increased cell death. Further investigation for identification of the signaling pathway revealed that PI3K and ERK signaling pathways are involved in bleomycin-induced fibrosis. Collectively, these results highlight that ALCAM plays a protective role in the pathogenesis of pulmonary fibrosis that inhibits epithelial cell apoptosis through the PI3K-Akt signaling pathway. Our findings demonstrate the potential of ALCAM as a therapeutic target for IPF and may aid the development of new strategies for the management and treatment of patients with IPF. |
| 게재정보 |
Am J Respir Cell Mol Biol. 2022 Apr;66(4):415-427 |
| 총저자명 |
Mi Na Kim, Jung Yeon Hong, Eun Gyul Kim, Jae Woo Lee, Soo Yeon Lee, Kyung Won Kim, Hyo Sup Shim, Chun Geun Lee, Jack A Elias, Yong Ju Lee, Myung Hyun Sohn
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