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- Title
Protein Kinase CK2 Regulates Nerve/Glial Antigen (NG)2-Mediated Angiogenic Activity of Human Pericytes.
- Authors
Schmitt, Beate M.; Boewe, Anne S.; Becker, Vivien; Nalbach, Lisa; Gu, Yuan; Götz, Claudia; Menger, Michael D.; Laschke, Matthias W.; Ampofo, Emmanuel
- Abstract
Protein kinase CK2 is a crucial regulator of endothelial cell proliferation, migration and sprouting during angiogenesis. However, it is still unknown whether this kinase additionally affects the angiogenic activity of other vessel-associated cells. In this study, we investigated the effect of CK2 inhibition on primary human pericytes. We found that CK2 inhibition reduces the expression of nerve/glial antigen (NG)2, a crucial factor which is involved in angiogenic processes. Reporter gene assays revealed a 114 bp transcriptional active region of the human NG2 promoter, whose activity was decreased after CK2 inhibition. Functional analyses demonstrated that the pharmacological inhibition of CK2 by CX-4945 suppresses pericyte proliferation, migration, spheroid sprouting and the stabilization of endothelial tubes. Moreover, aortic rings of NG2−/− mice showed a significantly reduced vascular sprouting when compared to rings of NG2+/+ mice, indicating that NG2 is an important regulator of the angiogenic activity of pericytes. In vivo, implanted Matrigel plugs containing CX-4945-treated pericytes exhibited a lower microvessel density when compared to controls. These findings demonstrate that CK2 regulates the angiogenic activity of pericytes through NG2 gene expression. Hence, the inhibition of CK2 represents a promising anti-angiogenic strategy, because it does not only target endothelial cells, but also vessel-associated pericytes.
- Subjects
PROTEIN kinase CK2; PERICYTES; ENDOTHELIAL cells; REPORTER genes; ANTIGENS; ENDOSTATIN
- Publication
Cells (2073-4409), 2020, Vol 9, Issue 6, p1546
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells9061546