Edil3, also known as EGF-like repeats and discoidin I-like domains 3 (EDIL3/Del-1), is a secreted protein involved in multiple biological processes. It plays a role in embryonic development and is associated with various physiological functions such as macrophage efferocytosis, neutrophil adhesion regulation, and angiogenesis [2,3,5]. It is involved in pathways like Toll-like receptor 9, αvβ3-FAK/MEK/ERK axis, and LC3-associated phagocytosis [1,2,4].

In myocardial infarction, Edil3 -/- mice showed improved post-MI adverse remodelling with lower mortality, better cardiac function, etc. This was due to enhanced neutrophil recruitment and pro-inflammatory macrophage polarization via the neutrophil extracellular traps (NETs)-Toll-like receptor 9 pathway [1]. In thoracic aortic dissection, global edil3 knockout mice had exacerbated disease with increased apoptotic vascular smooth muscle cells, as edil3-deficient phagocytes had inefficient internalization and degradation of apoptotic cells [2]. In psoriasis, injecting recombinant EDIL3 protein accelerated the disease process in mouse models, and EDIL3 was involved in angiogenesis via the αvβ3-FAK/MEK/ERK signal pathway [4]. In psoriatic arthritis, Edil3 knockout mice had a more severe phenotype, and recombinant EDIL3 protein injection alleviated the disease by regulating the activation of monocyte-derived DCs and Th17 cells [6].

In conclusion, Edil3 is a multifunctional protein. Its knockout mouse models have revealed its important roles in cardiac remodelling after myocardial infarction, prevention of aortic dissection, psoriasis-associated angiogenesis, and psoriatic arthritis development. These findings provide insights into potential therapeutic targets for these diseases.

References:

1. Wei, Xiaoqiong, Zou, Song, Xie, Zhonghui, Cui, Kaijun, Li, Jiong. . EDIL3 deficiency ameliorates adverse cardiac remodelling by neutrophil extracellular traps (NET)-mediated macrophage polarization. In Cardiovascular research, 118, 2179-2195. doi:10.1093/cvr/cvab269. https://pubmed.ncbi.nlm.nih.gov/34375400/

2. Yin, Zheng, Zhang, Jishou, Zhao, Mengmeng, Wan, Jun, Wang, Menglong. 2024. EDIL3/Del-1 prevents aortic dissection through enhancing internalization and degradation of apoptotic vascular smooth muscle cells. In Autophagy, 20, 2405-2425. doi:10.1080/15548627.2024.2367191. https://pubmed.ncbi.nlm.nih.gov/38873925/

3. Tabasum, Saba, Thapa, Dinesh, Giobbie-Hurder, Anita, Barbie, David A, Hodi, F Stephen. . EDIL3 as an Angiogenic Target of Immune Exclusion Following Checkpoint Blockade. In Cancer immunology research, 11, 1493-1507. doi:10.1158/2326-6066.CIR-23-0171. https://pubmed.ncbi.nlm.nih.gov/37728484/

4. Niu, Xuping, Han, Qixin, Li, Xinhua, Wu, Yan, Zhang, Kaiming. 2022. EDIL3 influenced the αvβ3-FAK/MEK/ERK axis of endothelial cells in psoriasis. In Journal of cellular and molecular medicine, 26, 5202-5212. doi:10.1111/jcmm.17544. https://pubmed.ncbi.nlm.nih.gov/36065978/

5. Niu, Xuping, Han, Qixin, Liu, Yanmin, Li, Junqin, Zhang, Kaiming. 2020. Psoriasis-associated angiogenesis is mediated by EDIL3. In Microvascular research, 132, 104056. doi:10.1016/j.mvr.2020.104056. https://pubmed.ncbi.nlm.nih.gov/32795468/

6. Yu, Jiadong, Wang, Xiaoyan, Zhou, Yifan, Cui, Kaijun, Li, Jiong. 2024. EDIL3 alleviates Mannan-induced psoriatic arthritis by slowing the intracellular glycolysis process in mononuclear-derived dendritic cells. In Inflammation, , . doi:10.1007/s10753-024-02134-y. https://pubmed.ncbi.nlm.nih.gov/39289212/