Del-1, an Endogenous Inhibitor of TGF-β Activation, Attenuates Fibrosisopen access
- Authors
- Kim, Dong-Young; Lee, Seung-Hwan; Fu, Yan; Jing, Feifeng; Kim, Won-Young; Hong, Sang-Bum; Song, Jung-A; Choe, Han; Ryu, Hyun Jin; Kim, Minjung; Lim, Dahae; Kim, Min-Seon; Yun, Chae-Ok; Lee, Taewon; Hyun, Hoon; Choi, Eun Young
- Issue Date
- Feb-2020
- Publisher
- Frontiers Media S.A.
- Keywords
- Del-1 (developmental endothelial locus-1); fibrosis; inflammation; integrins; transforming growth factor-beta activation
- Citation
- Frontiers in Immunology, v.11
- Journal Title
- Frontiers in Immunology
- Volume
- 11
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/44302
- DOI
- 10.3389/fimmu.2020.00068
- ISSN
- 1664-3224
1664-3224
- Abstract
- Uncontrolled activation of transforming growth factor (TGF)-β results in a wide range of pathologic conditions. Therapeutic interventions to regulate TGF-β signaling during fibrosis have been developed but the effectiveness is still limited. Here, we show that developmental endothelial locus-1 (Del-1) ameliorates fibrosis in mice by inhibiting αv integrin-mediated activation of TGF-β. Del-1 bound to αvβ6 integrin, an important activator of TGF-β, and inhibited the binding of αvβ6 integrin to the latency-associated peptide (LAP), thereby suppressing αv integrin-mediated activation of TGF-β. Lack of Del-1 increased colocalization of αv integrin and LAP in the lungs, which was reversed by Del-1 supplementation. The crucial role of Del-1 in regulating TGF-β activity was recapitulated in a mouse model of fibrosis using an adenovirus expressing inactive TGF-β1. Del-1 supplementation improved the pathological characteristics of the mice and reduced mortality. Thus, we propose that Del-1 is a negative regulator of TGF-β activation and a potential anti-fibrotic factor. © Copyright © 2020 Kim, Lee, Fu, Jing, Kim, Hong, Song, Choe, Ryu, Kim, Lim, Kim, Yun, Lee, Hyun and Choi.
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