AUTHOR=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 

TITLE=Del-1, an Endogenous Inhibitor of TGF-β Activation, Attenuates Fibrosis

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00068

DOI=10.3389/fimmu.2020.00068

ISSN=1664-3224

ABSTRACT=<p>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 α<sub>v</sub> integrin-mediated activation of TGF-β. Del-1 bound to α<sub>v</sub>β<sub>6</sub> integrin, an important activator of TGF-β, and inhibited the binding of α<sub>v</sub>β<sub>6</sub> integrin to the latency-associated peptide (LAP), thereby suppressing α<sub>v</sub> integrin-mediated activation of TGF-β. Lack of Del-1 increased colocalization of α<sub>v</sub> 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.</p>