Protein kinase CK2 is a regulator of angiogenesis in endometriotic lesions

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This study found that inhibiting protein kinase CK2 with quinalizarin reduced vascularization and lesion size in mouse models of endometriosis by impairing sprouting and functional capillary density.

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The study investigated whether protein kinase CK2 regulates angiogenesis in endometriotic lesions by testing the anti-angiogenic activity of the CK2 inhibitor quinalizarin. In rat aortic ring assays and in vivo using a dorsal skinfold chamber mouse model with induced endometriotic lesions, the authors assessed vascular sprouting and lesion vascularization using intravital fluorescence microscopy and histology, and measured CK2 activity and subunit expression in endometrial tissue. Quinalizarin inhibited vascular sprouting dose-dependently and reduced CK2 activity in endometrial tissue without changing expression of CK2 subunits α, α′, and β, and treated mice showed decreased vascularized area, lower functional capillary density, smaller lesion size, and reduced glandular fraction. This paper is centrally about endometriosis — it directly tests CK2 inhibition and demonstrates CK2 as a regulator of angiogenesis within endometriotic lesions.

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Abstract

Endometriosis is a frequent gynecological disease, which is crucially dependent on the process of angiogenesis. However, the underlying regulatory mechanisms of blood vessel development are still poorly understood. CK2 is a pleiotropic protein kinase, which is implicated in the regulation of various cellular processes including angiogenesis. Herein we studied for the first time the function of protein kinase CK2 in angiogenesis of endometriotic lesions. For this purpose, we analyzed the anti-angiogenic activity of the CK2 inhibitor quinalizarin in a rat aortic ring assay and its effect on the expression of individual CK2 subunits and on kinase activity in endometrial tissue. Moreover, endometriotic lesions were induced in dorsal skinfold chambers of quinalizarin- and vehicle-treated C57BL/6 mice to study their vascularization and morphology by means of repetitive intravital fluorescence microscopy and histology. Our results demonstrate that quinalizarin dose-dependently inhibits vascular sprouting. In addition, treatment of endometrial tissue with quinalizarin reduces CK2 activity without affecting the expression of the three CK2 subunits α, α' and β. In the dorsal skinfold chamber model of endometriosis, quinalizarin inhibits the vascularization of endometriotic lesions, which exhibit a significantly decreased vascularized area and functional capillary density when compared to those of vehicle-treated controls. This is associated with a reduced lesion size and histological fraction of endometrial glands. These findings indicate that CK2 is a regulator of angiogenesis in endometriotic lesions. Accordingly, inhibition of CK2 represents a novel option in the development of anti-angiogenic strategies for the treatment of endometriosis.
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Abstract

Endometriosis is a frequent gynecological disease, which is crucially dependent on the process of angiogenesis. However, the underlying regulatory mechanisms of blood vessel development are still poorly understood. CK2 is a pleiotropic protein kinase, which is implicated in the regulation of various cellular processes including angiogenesis. Herein we studied for the first time the function of protein kinase CK2 in angiogenesis of endometriotic lesions. For this purpose, we analyzed the anti-angiogenic activity of the CK2 inhibitor quinalizarin in a rat aortic ring assay and its effect on the expression of individual CK2 subunits and on kinase activity in endometrial tissue. Moreover, endometriotic lesions were induced in dorsal skinfold chambers of quinalizarin- and vehicle-treated C57BL/6 mice to study their vascularization and morphology by means of repetitive intravital fluorescence microscopy and histology. Our results demonstrate that quinalizarin dose-dependently inhibits vascular sprouting. In addition, treatment of endometrial tissue with quinalizarin reduces CK2 activity without affecting the expression of the three CK2 subunits α, α′ and β. In the dorsal skinfold chamber model of endometriosis, quinalizarin inhibits the vascularization of endometriotic lesions, which exhibit a significantly decreased vascularized area and functional capillary density when compared to those of vehicle-treated controls. This is associated with a reduced lesion size and histological fraction of endometrial glands. These findings indicate that CK2 is a regulator of angiogenesis in endometriotic lesions. Accordingly, inhibition of CK2 represents a novel option in the development of anti-angiogenic strategies for the treatment of endometriosis. Similar content being viewed by others

References

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They were approved by the local governmental animal care committee and were conducted in accordance with the German legislation on protection of animals and the NIH Guidelines for the Care and Use of Laboratory Animals (NIH Publication #85-23 Rev. 1985). Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Feng, D., Welker, S., Körbel, C. et al. Protein kinase CK2 is a regulator of angiogenesis in endometriotic lesions. Angiogenesis 15, 243–252 (2012). https://doi.org/10.1007/s10456-012-9256-2 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s10456-012-9256-2

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endometriosis

MeSH descriptors

Casein Kinase II Endometriosis Endometrium Neovascularization, Pathologic Animals Aorta Aorta Aorta Casein Kinase II Endometriosis Endometriosis Endometrium Endometrium Female Mice Neovascularization, Pathologic Neovascularization, Pathologic Rats Rats, Sprague-Dawley

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