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This study investigated the expression levels and functional roles of stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4 in human endometriosis. Researchers compared 50 patients with endometriosis against 50 controls with uterine fibroids, analyzing tissue samples and peritoneal fluid using RT-PCR, ELISA, and immunohistochemistry. The results demonstrated that both SDF-1 and CXCR-4 were significantly upregulated in endometriosis lesions and peritoneal fluid compared to normal endometrial tissue and control groups. In vitro experiments further revealed that SDF-1 promoted the proliferation of endometrial stromal cells in a dose-dependent manner, an effect that was inhibited by neutralizing antibodies against CXCR-4. This paper is centrally about endometriosis — specifically investigating the molecular mechanisms involving SDF-1/CXCR-4 signaling in lesion development and cell proliferation.
Abstract
Objective: To investigate the expressions and significances of SDF-1 and its receptor CXCR-4 in endometriosis. Methods: 50 hysteromyoma patients treated at Beijing Tongren Hospital, Capital Medical University between 1(st) January 2016 and 31(st) December 2017 were divided into control group, that is, non-endometriosis group, while another 50 endometriosis patients were divided into experimental group.The endometrial tissues, endometriosis lesions, and peritoneal fluid samples of hysteromyoma patients were collected by operation.RT-PCR, ELISA and immunohistochemistry were adopted to detect the expressions of SDF-1 and CXCR-4 in the two groups.Cell count was used to analyze the roles of SDF-1 and CXCR4 in the mitosis and proliferation of endometrial stromal cells. Results: The mean value of SDF-1 and CXCR-4 expressions in ascites or peritoneal fluid of endometriosis patients were (2.56±0.33) mg/L and (4.47±0.32) mg/L, respectively. The mean concentrations in ascites or peritoneal fluid in hysteromyoma patients were (1.39±0.36) mg/L and (3.16±0.32) mg/L, respectively.The expressions of SDF-1 and CXCR-4 in ascites or peritoneal fluid of endometriosis patients were both significantly higher than those of patients in non-endometriosis group (P<0.05). SDF-1 and CXCR-4 were expressed in both endometriosis lesions and the glandular epithelial cells and mesenchymal cells of normal endometrial tissue.Positive staining sites were located in the cytoplasm.A value was used to calculate and analyze the expression of immune staining.The mean A value of SDF-1 and CXCR-4 in endometriosis group were 0.21±0.13 and 0.21±0.13, respectively, and the mean A value in normal endometrial tissues were 0.15±0.13 and 0.14±0.13, respectively.The expressions of these two in endometrial tissues were significantly higher than that in normal endometrial tissues, and the differences were statistically significant (P<0.05). The expression of CXCR-4 mRNA was abundant in the mesenchymal cells of endometriosis cultured in vitro.SDF-1 promoted the mitosis and proliferation of endometrial stromal cells cultured in vitro in a dose-dependent manner.The neutralizing antibody against CXCR-4 was obviously inhibited. Conclusion: The high expressions of SDF-1 and CXCR-4 in endometriosis as well as SDF-1 through its specific receptor CXCR-4 promoted the mitosis and proliferation of endometrial stromal cells, suggesting that SDF-1 and CXCR-4 played important roles in the pathogenesis of endometriosis.
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基质细胞衍生因子-1和趋化因子受体-4在子宫内膜异位症患者病灶中的表达及意义
The expressions and the roles of SDF-1/CXCR-4 and SDF-1/CXCR-4 in human endometriosis
摘要目的 探讨基质细胞衍生因子-1(SDF-1)和趋化因子受体-4(CXCR-4)在子宫内膜异位症(EM)中的表达及意义.方法 选取2016年1月1日至2017年12月31日在首都医科大学附属北京同仁医院手术治疗的50例子宫肌瘤患者为对照组即非EM组,50例EM患者为试验组.经手术收集子宫肌瘤患者的子宫内膜组织、卵巢子宫内膜异位病灶组织和腹腔液标本.采用RT-PCR法、ELISA法、免疫组化法检测 SDF-1 和 CXCR-4 在二组的表达情况.采用 CCK-8 法检测 SDF-1 和CXCR-4在子宫内膜异位间质细胞分裂增殖中的作用.结果 SDF-1和CXCR-4在EM患者腹水或腹腔液中的浓度的平均值分别是(2.56 ±0.33) mg/L和(4.47 ±0.32) mg/L.在子宫肌瘤患者腹水或腹腔液中浓度的平均值分别是(1.39 ±0.36) mg/L和(3.16 ±0.32) mg/L. SDF-1和CXCR-4在子宫内膜异位症患者腹水或腹腔液中的表达均明显高于非EM组( P＜0.05). SDF-1和CXCR-4在EM病灶和正常子宫内膜组织中的腺上皮细胞和间质细胞中均有表达,免疫染色阳性部位均定位于细胞质.免疫染色的表达量采用吸光度值来计算分析及比较. EM组SDF-1和CXCR-4的平均值分别是0.21 ±0.13和0.21 ±0.13,正常子宫内膜组织中的平均值分别是0.15 ±0.13和0.14 ±0.13.两者在EM组织中的表达均明显高于正常子宫内膜组织,差异均有统计学意义(均P＜0.05).体外分离培养的EM间质细胞中有丰富的CXCR-4 mRNA的表达. SDF-1呈剂量依赖性促进体外培养的子宫内膜异位间质细胞的分裂增殖.其作用可使CXCR-4的中和抗体明显抑制.结论 SDF-1和CXCR-4在EM中的高表达及SDF-1通过其特异性受体CXCR-4促进了子宫内膜异位间质细胞的分裂增殖,提示,两者在EM的发病机制中扮演了重要的角色.
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abstractsObjective To investigate the expressions and significances of SDF-1 and its receptor CXCR-4 in endometriosis.Methods 50 hysteromyoma patients treated at Beijing Tongren Hospital , Capital Medical University between 1st January 2016 and 31st December 2017 were divided into control group , that is, non-endometriosis group, while another 50 endometriosis patients were divided into experimental group.The endometrial tissues, endometriosis lesions , and peritoneal fluid samples of hysteromyoma patients were collected by operation.RT-PCR, ELISA and immunohistochemistry were adopted to detect the expressions of SDF-1 and CXCR-4 in the two groups.Cell count was used to analyze the roles of SDF-1 and CXCR4 in the mitosis and proliferation of endometrial stromal cells .Results The mean value of SDF-1 and CXCR-4 expressions in ascites or peritoneal fluid of endometriosis patients were (2.56 ±0.33) mg/L and (4.47 ±0.32) mg/L, respectively.The mean concentrations in ascites or peritoneal fluid in hysteromyoma patients were (1.39 ±0.36) mg/L and (3.16 ±0.32) mg/L, respectively.The expressions of SDF-1 and CXCR-4 in ascites or peritoneal fluid of endometriosis patients were both significantly higher than those of patients in non-endometriosis group (P＜0.05).SDF-1 and CXCR-4 were expressed in both endometriosis lesions and the glandular epithelial cells and mesenchymal cells of normal endometrial tissue .Positive staining sites were located in the cytoplasm.A value was used to calculate and analyze the expression of immune staining.The mean A value of SDF-1 and CXCR-4 in endometriosis group were 0.21 ±0.13 and 0.21 ±0.13, respectively, and the mean A value in normal endometrial tissues were 0.15 ±0.13 and 0.14 ±0.13, respectively.The expressions of these two in endometrial tissues were significantly higher than that in normal endometrial tissues , and the differences were statistically significant ( P ＜0.05 ) .The expression of CXCR-4 mRNA was abundant in the mesenchymal cells of endometriosis cultured in vitro .SDF-1 promoted the mitosis and proliferation of endometrial stromal cells cultured in vitro in a dose-dependent manner.The neutralizing antibody against CXCR-4 was obviously inhibited.Conclusion The high expressions of SDF-1 and CXCR-4 in endometriosis as well as SDF-1 through its specific receptor CXCR-4 promoted the mitosis and proliferation of endometrial stromal cells , suggesting that SDF-1 and CXCR-4 played important roles in the pathogenesis of endometriosis .
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