Clec14a, a single-pass transmembrane glycoprotein belonging to the vascular expressed C-type lectin family, is specifically expressed in vascular endothelial cells during embryogenesis. It plays important roles in angiogenesis-related pathways, which are crucial for various biological processes like embryonic development, tissue repair, and tumor growth [2,3,4,5]. Genetic models, such as knockout mice, have been valuable in understanding its functions.

In Clec14a-deficient (Clec14a-KO) mice, ischemic stroke-related studies showed that the deficiency exacerbates neuronal loss. This is due to increased blood-brain barrier permeability and inflammation, likely through activation of the VEGF-A/VEGFR-2 signaling pathway [1]. In a mouse model of adriamycin-induced nephropathy, Clec14a deficiency exacerbated podocyte injury and proteinuria, along with enhanced inflammatory cell infiltration [2]. In zebrafish, the clec14a mutant embryos had partial defects and delay in the sprouting of intersegmental vessels, indicating its role in vasculogenesis and angiogenesis [4]. Also, in mice, blocking the CLEC14A-MMRN2 binding inhibited sprouting angiogenesis and tumour growth [5].

In conclusion, Clec14a is essential for maintaining the integrity of the blood-brain barrier, protecting podocytes, and promoting vasculogenesis and angiogenesis. The study of Clec14a-KO mouse models has provided insights into its role in ischemic stroke, focal segmental glomerular sclerosis, and tumor-related angiogenesis, highlighting its potential as a therapeutic target in these disease areas.

References:

1. Kim, Yeomyeong, Lee, Sungwoon, Zhang, Haiying, Kim, Young-Myeong, Kwon, Young-Guen. 2020. CLEC14A deficiency exacerbates neuronal loss by increasing blood-brain barrier permeability and inflammation. In Journal of neuroinflammation, 17, 48. doi:10.1186/s12974-020-1727-6. https://pubmed.ncbi.nlm.nih.gov/32019570/

2. Su, Zeyu, Li, Yujia, Lv, Hang, Wang, Xiaojie, Yi, Fan. . CLEC14A protects against podocyte injury in mice with adriamycin nephropathy. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 35, e21711. doi:10.1096/fj.202100283R. https://pubmed.ncbi.nlm.nih.gov/34107098/

3. Jang, Jihye, Kim, Mi Ra, Kim, Taek-Keun, Heo, Kyun, Lee, Sukmook. 2017. CLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis. In Scientific reports, 7, 10666. doi:10.1038/s41598-017-11118-y. https://pubmed.ncbi.nlm.nih.gov/28878328/

4. Pociute, Karolina, Schumacher, Jennifer A, Sumanas, Saulius. 2019. Clec14a genetically interacts with Etv2 and Vegf signaling during vasculogenesis and angiogenesis in zebrafish. In BMC developmental biology, 19, 6. doi:10.1186/s12861-019-0188-6. https://pubmed.ncbi.nlm.nih.gov/30953479/

5. Noy, P J, Lodhia, P, Khan, K, Bacon, A, Bicknell, R. 2015. Blocking CLEC14A-MMRN2 binding inhibits sprouting angiogenesis and tumour growth. In Oncogene, 34, 5821-31. doi:10.1038/onc.2015.34. https://pubmed.ncbi.nlm.nih.gov/25745997/