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

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

Frontiers in immunology (2020-03-03)
Dong-Young Kim, Seung-Hwan Lee, Yan Fu, Feifeng Jing, Won-Young Kim, Sang-Bum Hong, Jung-A Song, Han Choe, Hyun Jin Ryu, Minjung Kim, Dahae Lim, Min-Seon Kim, Chae-Ok Yun, Taewon Lee, Hoon Hyun, Eun Young Choi
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Triton X-114, laboratory grade
Sigma-Aldrich
5-Bromo-4-chloro-3-indolyl β-D-galactopyranoside, ≥98%, powder
Sigma-Aldrich
Bleomycin sulfate from Streptomyces verticillus, crystalline, 1.5-2.0 U/mg
Sigma-Aldrich
Anti-Integrin αVβ6 Antibody, clone 10D5, azide free, clone 10D5, Chemicon®, from mouse
Sigma-Aldrich
Human Small Airway Epithelial Cells (HSAEpC), 500,000 cryopreserved cells