Emcn, also known as endomucin, is an endothelial-specific glycocalyx component. It plays crucial roles in angiogenesis and the regulation of vascular-related functions. In the context of bone, it is associated with the CD31hiEMCNhi vascular endothelium which is involved in coupling angiogenesis and osteogenesis, and factors like SLIT3, PDGF-BB are associated with the regulation of this endothelium [1,2,4]. In tumor metastasis, its deficiency in endothelial cells can promote lung metastasis through affecting the pre-metastatic niche [3].

In mouse models, global knockout of Emcn (EMCN-/-mice) led to glomerular impairment, with increased infiltration of CD45 + cells, albuminuria, and abnormal podocyte and endothelial ultrastructure, suggesting its role in maintaining glomerular filtration barrier structure and function [5]. In endothelial-specific knockout of Emcn (EMCNecko) mice, it was found that endothelial EMCN deficiency did not significantly affect primary tumor growth but strongly promoted spontaneous metastasis, revealing its role in tumor lung metastasis [3].

In conclusion, Emcn is essential for maintaining normal vascular-related functions such as in bone angiogenesis, glomerular integrity, and tumor metastasis regulation. The gene knockout mouse models have significantly contributed to understanding its functions in these disease-related areas, providing insights into potential therapeutic targets for conditions like osteoporosis, glomerular diseases, and tumor metastasis.

References:

1. Xu, Ren, Yallowitz, Alisha, Qin, An, Glimcher, Laurie H, Greenblatt, Matthew B. 2018. Targeting skeletal endothelium to ameliorate bone loss. In Nature medicine, 24, 823-833. doi:10.1038/s41591-018-0020-z. https://pubmed.ncbi.nlm.nih.gov/29785024/

2. Peng, Yi, Wu, Song, Li, Yusheng, Crane, Janet L. 2020. Type H blood vessels in bone modeling and remodeling. In Theranostics, 10, 426-436. doi:10.7150/thno.34126. https://pubmed.ncbi.nlm.nih.gov/31903130/

3. Zhang, Guoxin, Li, Mengyuan, Zhou, Dandan, Zhang, Wenlong, Gao, Ran. 2022. Loss of endothelial EMCN drives tumor lung metastasis through the premetastatic niche. In Journal of translational medicine, 20, 446. doi:10.1186/s12967-022-03649-4. https://pubmed.ncbi.nlm.nih.gov/36184589/

4. Xie, Hui, Cui, Zhuang, Wang, Long, Liao, Eryuan, Cao, Xu. 2014. PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. In Nature medicine, 20, 1270-8. doi:10.1038/nm.3668. https://pubmed.ncbi.nlm.nih.gov/25282358/

5. Hu, Zhengping, Cano, Issahy, Lei, Fengyang, Ng, Yin Shan Eric, D'Amore, Patricia A. 2024. Loss of the Endothelial Glycocalyx Component EMCN Leads to Glomerular Impairment. In Circulation research, 136, 59-74. doi:10.1161/CIRCRESAHA.124.325218. https://pubmed.ncbi.nlm.nih.gov/39584795/