Data from: Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development

Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF) appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO) mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT) mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2), cell adhesion (αv and β3 integrins), survival (B-cell lymphoma-2) and angiogenic (vascular endothelial cell growth) factorsrelevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis.盆腔炎是子宫内膜异位症发病机制的标志性特征，亦是该疾病症状的主要诱因。异常的免疫与炎症改变不仅会加重子宫内膜异位症的核心症状，还可促进异位子宫内膜组织的增殖与子宫内膜异位症的发生发展。研究发现，在子宫内膜异位症患者腹腔液中表达升高的主要促炎因子——巨噬细胞移动抑制因子（macrophage migration inhibitory factor, MIF），在腹腔巨噬细胞及异位、高血管化的早期子宫内膜异位病灶中呈过表达且活化状态；体外实验证实，MIF可诱导子宫内膜异位病灶细胞产生血管生成、炎症及雌激素生成表型，体内实验则提示其可能成为潜在治疗靶点。本研究采用MIF基因敲除（KO）小鼠模型，将MIF-KO或同基因野生型（WT）小鼠的子宫内膜组织腹腔注射至MIF-KO小鼠体内，反之亦然；结果显示，MIF基因缺失可显著抑制异位子宫内膜组织的生长，破坏病灶组织结构，并显著下调与子宫内膜异位症发病机制相关的主要炎症因子（环氧合酶-2）、细胞黏附因子（αv及β3整合素）、存活因子（B细胞淋巴瘤-2）及血管生成因子（血管内皮细胞生长）的表达；而向MIF-KO小鼠回补MIF后，子宫内膜异位样病灶的数量与大小均得到显著恢复。有趣的是，交叉实验结果表明，异位子宫内膜组织的生长需要子宫内膜组织与腹腔宿主组织均存在MIF，这提示MIF参与了子宫内膜-腹腔的相互作用。本研究有力证实了MIF在子宫内膜异位症发生发展中的关键作用，为子宫内膜异位症的靶向治疗提供了重要的潜在研究价值。