Endometriosis is a disease characterized by implants of endometrial tissue outside the uterine cavity and is strongly associated with infertility. Focal adhesion of endometrial tissue to the peritoneum is an indication of incipient endometriosis. In this study, we examined the effect of various cytokines that are known to be involved in the pathology of endometriosis on endometrial cell adhesion. Among the investigated cytokines, transforming growth factor-β1 (TGF-β1) increased adhesion of endometrial cells to the mesothelium through induction of α2-6 sialylation. The expression levels of β-galactoside α2-6 sialyltransferase (ST6Gal) 1 and ST6Gal2 were increased through activation of TGF-βRI/SMAD2/3 signaling in endometrial cells. In addition, we discovered that terminal sialic acid glycan epitopes of endometrial cells engage with sialic acid-binding immunoglobulin-like lectin-9 expressed on mesothelial cell surfaces. Interestingly, in an in vivo mouse endometriosis model, inhibition of endogenous sialic acid binding by a NeuAcα2-6Galβ1-4GlcNAc injection diminished TGF-β1-induced formation of endometriosis lesions. Based on these results, we suggest that increased sialylation of endometrial cells by TGF-β1 promotes the attachment of endometrium to the peritoneum, encouraging endometriosis outbreaks.

中文翻译：

---

子宫内膜细胞的α2-6唾液酸化增加导致子宫内膜异位症的发展。

子宫内膜异位症是一种以子宫腔外的子宫内膜组织植入为特征的疾病，与不孕症密切相关。子宫内膜组织与腹膜的局部粘附是初期子宫内膜异位症的指征。在这项研究中，我们检查了各种与子宫内膜异位症病理相关的细胞因子对子宫内膜细胞粘附的影响。在研究的细胞因子中，转化生长因子-β1（TGF-β1）通过诱导α2-6唾液酸化来增加子宫内膜细胞对间皮的粘附。β-半乳糖苷α2-6唾液酸转移酶（ST6Gal）1和ST6Gal2的表达水平通过激活子宫内膜细胞中的TGF-βRI/ SMAD2 / 3信号传导而增加。此外，我们发现子宫内膜细胞的末端唾液酸聚糖表位与间皮细胞表面表达的唾液酸结合免疫球蛋白样凝集素9结合。有趣的是，在体内小鼠子宫内膜异位症模型中，通过NeuAcα2-6Galβ1-4GlcNAc注射抑制内源性唾液酸结合可减少TGF-β1诱导的子宫内膜异位症形成。基于这些结果，我们认为，TGF-β1增强子宫内膜细胞的唾液酸化作用会促进子宫内膜对腹膜的附着，从而促进子宫内膜异位症的爆发。