EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) (DEL-1)

Developmental Endothelial Locus-1 (DEL-1), also known as EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3), is a 52-kDa extracellular matrix glycoprotein primarily secreted by endothelial cells, mesenchymal stem cells, and certain macrophages (UniProt, 2024; NIH, 2021). It plays a critical role in maintaining tissue homeostasis by regulating leukocyte recruitment and promoting the resolution of inflammation through efferocytosis (Frontiers in Immunology, 2022; Nature Immunology, 2019). DEL-1 acts as an endogenous inhibitor of the leukocyte adhesion cascade by binding to αLβ2 (LFA-1) and αMβ2 (Mac-1) integrins, thereby preventing the interaction between leukocytes and the vascular endothelium (NIH, 2021; Nature Immunology, 2019). In addition to its anti-inflammatory properties, DEL-1 is a potent angiogenic factor that interacts with αvβ3 and αvβ5 integrins to promote endothelial cell migration and vascular remodeling (UniProt, 2024; Frontiers in Immunology, 2022). In the context of disease, DEL-1 is often overexpressed in various cancers, such as gastric and hepatocellular carcinoma, where it promotes tumor angiogenesis and metastasis, making it a potential target for inhibition (NIH, 2021; Atlas of Genetics and Cytogenetics in Oncology and Haematology, 2014). Conversely, its anti-inflammatory and pro-resolving functions are being explored for the treatment of inflammatory conditions like periodontitis and cardiovascular diseases such as hypertension and ischemia (Frontiers in Immunology, 2022; Nature Immunology, 2019).

Other names

Developmental endothelial locus-1DEL1EDIL3Integrin-binding protein DEL1EGF-like repeat and discoidin I-like domain-containing protein 3

DEL-1 functions as a multi-domain bridging molecule that interacts with various integrin receptors. It inhibits leukocyte recruitment by competitively binding to the αLβ2 (LFA-1) and αMβ2 (Mac-1) integrins on leukocytes, thereby blocking their interaction with ICAM-1 on the endothelium (Nature Immunology, 2019). Additionally, DEL-1 promotes the clearance of apoptotic cells (efferocytosis) by acting as a bridge between phosphatidylserine on apoptotic cells and αvβ3 integrin on phagocytes (Nature Immunology, 2019). It also stimulates angiogenesis by binding to αvβ3 and αvβ5 integrins on endothelial cells, triggering pro-survival and migratory signaling pathways (UniProt, 2024; Frontiers in Immunology, 2022).