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 activates stromal cell–derived factor-1-CXCR4 to participate in estrogen-mediated endothelial progenitor cell homing to endometriosis.
Rong Zhao, M.M., Dilu Feng, M.D., Guobin Zhuang, M.D., Yan Liu, M.D., Shuqi Chi, M.D., Jun Zhang, M.D., Xing Zhou, M.D., Wei Zhang, M.M., Hongbo Wang, M.D.
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.
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.
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.
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.