Inhibition of protein kinase CK2 suppresses angiogenesis and hematopoietic stem cell recruitment to retinal neovascularization sites
Inhibition of protein kinase CK2 suppresses angiogenesis and hematopoietic stem cell recruitment to retinal neovascularization sites
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DOI：
10.1007/s11010-008-9831-4
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发表时间：
2008-09-01
影响因子：
4.3
通讯作者：
Ljubimov, A. V.
中科院分区：
文献类型：
--
作者：
Kramerov, A. A.;Saghizadeh, M.;Ljubimov, A. V.
无处不在的蛋白激酶CK2参与了多种关键的细胞功能。我们探讨了CK2在血管生成中的作用。如前所述，抑制CK2可减少内皮细胞的增殖、存活和迁移、管状形成和在Matrigel上的二次萌发。在增殖性视网膜病变的小鼠模型中，腹膜内注射CK2抑制剂显著减少视网膜前新生血管。在这个模型中，CK2抑制剂与生长抑素类似物奥曲肽具有相加作用，导致药物剂量显著减少，以达到同样的效果。因此，CK2抑制剂可能会成为未来旨在抑制病理性血管生成的有效药物。视网膜免疫染色显示CK2主要在星形胶质细胞中表达。在人类糖尿病视网膜中，所有CK2亚单位的mRNA水平下降，与细胞凋亡增加一致。重要的是，一种特定的CK2抑制剂阻止了骨髓来源的造血干细胞募集到视网膜新生血管区域。这可能为CK2抑制剂对新生血管的作用提供了新的机制。
Ubiquitous protein kinase CK2 participates in a variety of key cellular functions. We have explored CK2 involvement in angiogenesis. As shown previously, CK2 inhibition reduced endothelial cell proliferation, survival and migration, tube formation, and secondary sprouting on Matrigel. Intraperitoneally administered CK2 inhibitors significantly reduced preretinal neovascularization in a mouse model of proliferative retinopathy. In this model, CK2 inhibitors had an additive effect with somatostatin analog, octreotide, resulting in marked dose reduction for the drug to achieve the same effect. CK2 inhibitors may thus emerge as potent future drugs aimed at inhibiting pathological angiogenesis. Immunostaining of the retina revealed predominant CK2 expression in astrocytes. In human diabetic retinas, mRNA levels of all CK2 subunits decreased, consistent with increased apoptosis. Importantly, a specific CK2 inhibitor prevented recruitment of bone marrow-derived hematopoietic stem cells to areas of retinal neovascularization. This may provide a novel mechanism of action of CK2 inhibitors on newly forming vessels.