Frontiers in Immunology, 2020.11, 68-0, DOI: https://doi.org/10.3389/fimmu.2020.00068

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

Kim DY, Lee SH;Fu Y;Jing F;Kim WY;Hong SB;Song JA;Choe H;Ryu H;Kim M;Lim D;Kim MS;Yun CO;Lee T;Hyun H;Choi E

Abstract

Uncontrolled activation of transforming growth factor (TGF)-b results in a wide range of pathologic conditions. Therapeutic interventions to regulate TGF-b 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 av integrin-mediated activation of TGF-b. Del-1 bound to avb6 integrin, an important activator of TGF-b, and inhibited the binding of avb6 integrin to the latency-associated peptide (LAP), thereby suppressing av integrin-mediated activation of TGF-b. Lack of Del-1 increased colocalization of av integrin and LAP in the lungs, which was reversed by Del-1 supplementation. The crucial role of Del-1 in regulating TGF-b activity was recapitulated in a mouse model of fibrosis using an adenovirus expressing inactive TGF-b1. 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-b activation and a potential anti-fibrotic factor.

• DOI: https://doi.org/10.3389/fimmu.2020.00068
• ISBN or ISSN: 1664-3224

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.