| First Author | Kim DY | Year | 2020 |
| Journal | Front Immunol | Volume | 11 |
| Pages | 68 | PubMed ID | 32117240 |
| Mgi Jnum | J:305693 | Mgi Id | MGI:6705270 |
| Doi | 10.3389/fimmu.2020.00068 | Citation | Kim DY, et al. (2020) Del-1, an Endogenous Inhibitor of TGF-beta Activation, Attenuates Fibrosis. Front Immunol 11:68 |
| abstractText | Uncontrolled activation of transforming growth factor (TGF)-beta results in a wide range of pathologic conditions. Therapeutic interventions to regulate TGF-beta 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 alphav integrin-mediated activation of TGF-beta. Del-1 bound to alphavbeta6 integrin, an important activator of TGF-beta, and inhibited the binding of alphavbeta6 integrin to the latency-associated peptide (LAP), thereby suppressing alphav integrin-mediated activation of TGF-beta. Lack of Del-1 increased colocalization of alphav integrin and LAP in the lungs, which was reversed by Del-1 supplementation. The crucial role of Del-1 in regulating TGF-beta activity was recapitulated in a mouse model of fibrosis using an adenovirus expressing inactive TGF-beta1. 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-beta activation and a potential anti-fibrotic factor. |
