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  2. Protein kinase CK2 participates in estrogen-mediated endothelial progenitor cell homing to endometriotic lesions through stromal cells in a stromal cell-derived factor-1- CXCR4-dependent manner

Protein kinase CK2 participates in estrogen-mediated endothelial progenitor cell homing to endometriotic lesions through stromal cells in a stromal cell-derived factor-1- CXCR4-dependent manner

  • Fertil Steril. 2020 May;113(5):1067-1079.e5. doi: 10.1016/j.fertnstert.2019.12.035.
Rong Zhao 1 Dilu Feng 1 Guobin Zhuang 1 Yan Liu 1 Shuqi Chi 2 Jun Zhang 1 Xing Zhou 1 Wei Zhang 1 Hongbo Wang 3
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huang Zhong University of Science and Technology, Wuhan, People's Republic of China.
  • 2 Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
  • 3 Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huang Zhong University of Science and Technology, Wuhan, People's Republic of China. Electronic address: hb_wang1969@sina.com.
Abstract

Objective: To explore the possible mechanism of protein kinase CK2, which participates in estrogen recruitment of endothelial progenitor cells (EPCs), and its role in the angiogenesis of endometriosis lesions.

Design: Laboratory study.

Setting: University.

Animal(s): BALB/c mice.

Intervention(s): Exposure of human endometrial stromal cells (HESCs) to estrogen and CK2 Inhibitor CX-4945 and endometrial stromal cells transfected with the protein kinase CK2 vector (HESC-CK2). Endometriosis models were induced by allogeneic mice transplantation of the endometrium into dorsal skinfold chambers. The mice received an IP injection of 50 mg/kg emodin per day or were treated with 100 μg/kg estrogen by SC injection once a week.

Main outcome measure(s): The concentration of cytokines in cells was measured with ELISA. The migration of EPCs was examined using the scratch assay method and Transwell, a capillary tube-formation assay to determine EPC tube-forming capacity, and protein and mRNA expression with Western blot and polymerase chain reaction analyses, respectively.

Result(s): Protein kinase CK2 participates in estrogen-mediated EPC homing to endometriotic lesions through stromal cells in a stromal cell-derived factor-1 (SDF-1)-CXCR4-dependent manner. Conditioned medium from endometrial stromal cells that were stably transfected with the protein kinase CK2 vector (HESC-CK2) or pretreated with estrogen significantly enhanced the migration and recruitment of EPCs. In contrast, conditioned medium from HESCs that were treated with CX-4945, a selective inhibitor of CK2, inhibited the mobility and viability of EPCs. Furthermore, CK2 overexpression significantly upregulated SDF-1 expression and secretion in endometrial stromal cells by activating the Akt/mTOR pathway. Moreover, treatment with the SDF-1 receptor CXCR4-specific inhibitor AMD3100 completely reversed the CK2-enhanced migration of EPCs.

Conclusion(s): This study demonstrates that CK2 participates in estrogen-mediated EPC homing to endometriotic lesions through stromal cells in an SDF-1-CXCR4-dependent manner and may be a therapeutic target.

Keywords

Endometriosis; endothelial progenitor cell; neovascularization; protein kinase CK2.

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