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

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.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

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

doi

10.3389/fimmu.2020.00068

subject

Has Abstract

pub_date

2020-02-07 00:00:00

pages

68

issn

1664-3224

journal_volume

11

pub_type

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