Extracellular matrix metalloproteinase inducer expression in the baboon endometrium: menstrual cycle and endometriosis

Extracellular matrix metalloproteinase inducer expression in the baboon endometrium: menstrual cycle and endometriosis
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DOI:
10.1530/rep-09-0481
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发表时间:
2010-12-01
期刊:
影响因子:
3.8
通讯作者:
Nowak, R. A.
Nowak, R. A.
中科院分区:
生物学3区
文献类型:
--
作者:
Braundmeier, A. G.;Fazleabas, A. T.;Nowak, R. A.

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细胞外基质金属蛋白酶诱导剂(EMMPRIN, BSG)通过基质金属蛋白酶(MMPs)调控组织重塑。在人类和非人类灵长类动物中,子宫内膜重塑对月经和子宫内膜异位症的发病机制很重要。我们假设,与人类一样,BSG和MMPs在循环狒狒的子宫内膜中表达,并且它们的表达受卵巢激素的激素调节,但子宫内膜异位症破坏了这种调节。采用q-PCR和免疫组化检测BSG在狒狒子宫内膜中的表达。在对照循环动物子宫内膜中,BSG mRNA水平在分泌后期组织中最高。增殖期BSG蛋白定位于腺上皮细胞;分泌期组织中腺上皮和管腔上皮表达BSG,基质染色较弱。几个MMPs在整个月经周期中有差异表达,在月经期间表达水平最高。在切除卵巢的动物中,雌激素和孕激素联合处理的BSG子宫内膜mRNA水平高于单独雌激素处理。单独雌激素导致BSG蛋白主要定位于子宫内膜腺上皮,而雌激素和孕激素治疗显示BSG蛋白定位于腺细胞和间质细胞。与对照组相比,外源激素治疗导致所有MMPs的表达模式不同。在子宫内膜异位症动物的异位子宫内膜中,BSG mRNA水平和蛋白水平在疾病进展早期升高,但在疾病进展后期下降。与对照动物相比,子宫内膜异位症升高了除MMP7外的所有MMPs的表达。在狒狒中,BSG和mmp2的子宫内膜表达均受卵巢激素的调节,而它们的表达模式在子宫内膜异位症动物中是失调的。复制(2010)140 911-920
Extracellular matrix metalloproteinase inducer (EMMPRIN; BSG) regulates tissue remodeling through matrix metalloproteinases (MMPs). In human and non-human primates, endometrial remodeling is important for menstruation and the pathogenesis of endometriosis. We hypothesized that as in humans, BSG and MMPs are expressed in the endometrium of cycling baboons, and their expression is hormonally regulated by ovarian hormones, but endometriosis disrupts this regulation. BSG expression was evaluated in the baboon endometrium by q-PCR and immunohistochemistry. In the endometrium of control cycling animals, BSG mRNA levels were highest in late secretory stage tissue. BSG protein localized to glandular epithelial cells during the proliferative phase; whereas, secretory stage tissues expressed BSG in glandular and luminal epithelia with weak stromal staining. Several MMPs were differentially expressed throughout the menstrual cycle with the highest levels found during menstruation. In ovariectomized animals, BSG endometrial mRNA levels were highest with treatment of both estrogen and progesterone than that with only estrogen. Estrogen alone resulted in BSG protein localization primarily in the endometrial glandular epithelia, while estrogen and progesterone treatment displayed BSG protein localization in both the glandular and stromal cells. Exogenous hormone treatment resulted in differential expression patterns of all MMPs compared with the control cycling animals. In the eutopic endometrium of endometriotic animals, BSG mRNA levels and protein were elevated early but decreased later in disease progression. Endometriosis elevated the expression of all MMPs except MMP7 compared with the control animals. In baboons, BSG and MMPendometrial expression is regulated by both ovarian hormones, and their expression patterns are dysregulated in endometriotic animals. Reproduction (2010) 140 911-920