Department of Animal Sciences, University of Illinois, Urbana, IL 61801, USA.
Reprod Sci. 2012 Dec;19(12):1292-301. doi: 10.1177/1933719112450332. Epub 2012 Jun 22.
Endometrial remodeling is a physiological process involved in the gynecological disease, endometriosis. Tissue remodeling is directed by uterine fibroblast production of matrix metalloproteinases (MMPs). Several MMPs are regulated directly by the protein extracellular matrix metalloproteinase inducer (EMMPRIN) and also by proinflammatory cytokines such as interleukin (IL)1-α/β. We hypothesized that human uterine epithelial cells (HESs) secrete intact EMMPRIN to stimulate MMPs. Microvesicles from HES cell-conditioned medium (CM) expressed intact EMMPRIN protein. Treatment of HES cells with estradiol or phorbyl 12-myristate-13-acetate increased the release of EMMPRIN-containing microvesicles. The HES CM stimulated MMP-1, -2, and -3 messenger RNA levels in human uterine fibroblasts (HUFs) and EMMPRIN immunodepletion from HES-cell concentrated CM reduced MMP stimulation (P < .05). Treatment of HUF cells with low concentrations of IL-1β/α stimulated MMP production (P < .05). These results indicate that HES cells regulate MMP production by HUF cells by secretion of EMMPRIN, in response to ovarian hormones, proinflammatory cytokines as well as activation of protein kinase C.
子宫内膜重塑是一种涉及妇科疾病子宫内膜异位症的生理过程。组织重塑由子宫成纤维细胞产生的基质金属蛋白酶 (MMPs) 指导。几种 MMPs 直接受蛋白细胞外基质金属蛋白酶诱导因子 (EMMPRIN) 以及促炎细胞因子如白细胞介素 (IL)1-α/β 的调节。我们假设人子宫内膜上皮细胞 (HES) 会分泌完整的 EMMPRIN 来刺激 MMPs。HES 细胞条件培养基 (CM) 的微泡表达完整的 EMMPRIN 蛋白。用雌二醇或佛波醇 12-肉豆蔻酸 13-乙酸酯处理 HES 细胞会增加含有 EMMPRIN 的微泡的释放。HES CM 刺激人子宫成纤维细胞 (HUF) 中的 MMP-1、-2 和 -3 信使 RNA 水平，而从 HES 细胞浓缩 CM 中去除 EMMPRIN 会减少 MMP 刺激 (P <.05)。用低浓度的白细胞介素 1β/α 处理 HUF 细胞会刺激 MMP 产生 (P <.05)。这些结果表明，HES 细胞通过分泌 EMMPRIN 来调节 HUF 细胞的 MMP 产生，这是对卵巢激素、促炎细胞因子以及蛋白激酶 C 激活的反应。
