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
; 113(5): 1067-1079.e5, 2020 05.
Article
em En
| MEDLINE
| ID: mdl-32386617
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células Estromais
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Receptores CXCR4
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Caseína Quinase II
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Endometriose
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Endométrio
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Quimiocina CXCL12
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Células Progenitoras Endoteliais
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article