Bone Marrow Stem Cell Chemotactic Activity Is Induced by Elevated CXCl12 in Endometriosis
Bone Marrow Stem Cell Chemotactic Activity Is Induced by Elevated CXCl12 in Endometriosis
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DOI：
10.1177/1933719116672587
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发表时间：
2017-04-01
影响因子：
2.9
通讯作者：
Taylor, Hugh S.
中科院分区：
文献类型：
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作者：
Moridi, Irene;Mamillapalli, Ramanaiah;Taylor, Hugh S.
子宫内膜异位症是由子宫内膜组织在子宫外生长引起的炎症性妇科疾病。子宫内膜异位症产生趋化因子，包括CXCL 12，吸引骨髓细胞到病变。在这项研究中，我们描述的表达，定位和趋化活性的CXCL 12在炎症病变。从接受腹腔镜检查的子宫内膜异位症患者和非子宫内膜异位症患者的对照子宫内膜中收集活检标本。与在位子宫内膜相比，CXCl 12和CXCR 4信使RNA的表达在子宫内膜异位症中分别增加约4倍和6倍。免疫组化结果显示，CXCR 4在子宫内膜异位症和正常在位子宫内膜的间质和上皮中均有表达。与对照子宫内膜相比，子宫内膜异位病变的所有细胞区室中CXCR 4蛋白表达水平显著升高。CXCL 12蛋白表达也较高的增生性病变，是最大的上皮隔室。CXCL 12在培养的子宫内膜异位症的条件培养基中比对照组增加更多，如通过酶联免疫吸附测定所测量的。Transwell小室迁移用于证明与在位子宫内膜相比，在异位条件培养基中小鼠骨髓干细胞对CXCL 12的化学吸引力增加2倍。我们的研究结果表明，子宫内膜异位症优先募集干细胞可以解释子宫内膜异位症如何在募集有限的循环干细胞供应方面胜过在位子宫内膜。CXCL 12/CXCR 4信号轴是治疗子宫内膜异位症及其相关疾病的潜在靶点。
Endometriosis is an inflammatory gynecological disorder caused by the growth of endometrial tissue outside the uterus. Endometriosis produces chemokines, including CXCL12, that attract bone marrow cells to the lesions. In this study, we describe the expression, localization, and chemotactic activity of CXCL12 in endometriotic lesions. Biopsies were collected both from women with endometriosis undergoing laparoscopy and control endometrium from women without endometriosis. Expression of CXCl12 and CXCR4 messenger RNA was increased approximately 4- and 6-fold, respectively, in endometriosis compared to eutopic endometrium. Immunohistochemistry of lesions revealed that CXCR4 was expressed in the stroma and epithelium in both endometriosis and control eutopic endometrium. The level of CXCR4 protein expression was significantly higher in all cellular compartments of the endometriotic lesions compared to control endometrium. CXCL12 protein expression was also higher in endometriotic lesions and was greatest in the epithelial compartment. CXCL12 was increased more in the condition media of cultured endometriosis than in controls as measured by enzyme-linked immunosorbent assay. Transwell chamber migration was used to demonstrate 2-fold increased chemoattraction of mouse bone marrow stem cells toward CXCL12 in the endometriotic-conditioned medium compared with eutopic endometrium. Our results indicate that a preferential recruitment of stem cells to endometriosis can explain how endometriosis outcompetes eutopic endometrium in recruiting the limited supply of circulating stem cells. The CXCL12/CXCR4 signaling axis is a potential target for the treatment of endometriosis and its associated disorders.