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고려대학교

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Redox Biol., Feb 20 2025, 81 S2213-2317(25)00068-0 | https://doi.org/10.1016/j.redox.2025.103555 Identification of Tie2 as a sensor for reactive oxygen species and its therapeutic implication

An Vuong Quynh Pham ^a, Yongwoo Na ^b, Gyeongseo Suk ^a, Chansik Yang ^a, So Min Kang ^a, Joonha Lee ^a, Hongseo Choi ^c, Wook Kim ^c, Sung Wook Chi ^a, Sangyeul Han ^d, Hae Woong Choi ^a, Hyeonwoo Kim ^b,e, Chungho Kim ^a

^aDepartment of Life Sciences, Korea University, Seoul, 02841, Republic of Korea
^bDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea
^cDepartment of Molecular Science & Technology, Ajou University, Suwon, 16499, Republic of Korea
^dIngenia Therapeutics, 34 Coolidge Ave. 2nd Floor, Watertown, MA, 02472, United States
^eKAIST Stem Cell Center, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea

Corresponding author : Chungho Kim

Abstract

Psoriasis is a chronic inflammatory disease characterized by hyperproliferation of keratinocytes and abnormal blood vessels. As hyperproliferation is driven by pro-inflammatory cytokines produced by activated immune cells, therapeutic strategies often target these cytokines to manage the disease. However, the role of abnormally developed blood vessels has often been overlooked in treatment approaches. In this study, we focused on blood vessels in psoriatic lesions and investigated the potential interplay between immune and endothelial cells by adopting imiquimod treated mice as in vivo model, together with various cell biological, biochemical, and structural analyses. We found that activated immune cells can generate reactive oxygen species, subsequently inducing oxidative stress in endothelial cells. Oxidative stress impairs endothelial cell layer integrity, thereby facilitating transendothelial migration of immune cells. Mechanistically, oxidative conditions inhibit Tie2 activation, potentially by modifying its cysteine residues, leading to deactivation of its vessel-stabilizing functions. Additionally, we demonstrated that reactivating Tie2 under such conditions could restore endothelial barrier function and alleviate the disease. These results suggest that Tie2 serves as a receptor that is directly responsive to oxidative environments, thereby modulating its kinase activity. Furthermore, we suggest that Tie2 reactivation is a promising alternative therapeutic approach for psoriasis.

논문정보

형식Research article
게재일2025년 02월 (BRIC 등록일 2025-02-25)
연구진국내(교신)+국외 연구진
분야 생명과학 > 세포생물학

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