Uterine epithelial cell proliferation and endometrial hyperplasia: evidence from a mouse model
Uterine epithelial cell proliferation and endometrial hyperplasia: evidence from a mouse model
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DOI：
10.1093/molehr/gau033
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发表时间：
2014-08-01
影响因子：
4
通讯作者：
Li, Qinglei
中科院分区：
文献类型：
--
作者：
Gao, Yang;Li, Shu;Li, Qinglei
在子宫中，上皮细胞增殖在动情周期和怀孕期间发生变化。不受控制的上皮细胞增殖导致植入失败和/或癌症发展。转化生长因子-β（TGF-β）信号传导是多种生物过程的基本调节剂，并且对于多种生殖功能是不可或缺的。然而，TGF-β信号在子宫上皮细胞中的体内作用仍然不清楚。我们已经证明，在子宫中，使用抗苗勒管激素受体2型（Amhr 2）Cre条件性缺失TGF-β 1型受体（Tgfbr 1）导致子宫肌层缺陷。在这里，我们描述了增强上皮细胞增殖Ki 67在这些小鼠子宫的免疫染色。在老年女性中，这种异常最终导致子宫内膜增生。为了排除卵巢类固醇激素的潜在影响，在卵巢切除术后评估子宫上皮细胞的增殖状态。在卵巢切除的Tgfbr 1 Amhr 2-Cre条件性基因敲除小鼠中也发现子宫上皮细胞增殖增加。我们进一步证明了成纤维细胞生长因子10（Fgf 10）的转录水平显着上调Tgfbr 1 Amhr 2-Cre条件敲除子宫。同样，用TGF-β 1处理原代子宫基质细胞显著降低Fgf 10 mRNA表达。因此，我们的研究结果表明，TGFBR 1介导的信号在调节子宫上皮细胞增殖的潜在参与，并提供遗传证据支持子宫上皮细胞增殖在子宫内膜增生症的发病机制中的作用。
In the uterus, epithelial cell proliferation changes during the estrous cycle and pregnancy. Uncontrolled epithelial cell proliferation results in implantation failure and/or cancer development. Transforming growth factor-beta (TGF-beta) signaling is a fundamental regulator of diverse biological processes and is indispensable for multiple reproductive functions. However, the in vivo role of TGF-beta signaling in uterine epithelial cells remains poorly defined. We have shown that in the uterus, conditional deletion of the Type 1 receptor for TGF-beta (Tgfbr1) using anti-Mullerian hormone receptor type 2 (Amhr2) Cre leads to myometrial defects. Here, we describe enhanced epithelial cell proliferation by immunostaining of Ki67 in the uteri of these mice. The aberration culminated in endometrial hyperplasia in aged females. To exclude the potential influence of ovarian steroid hormones, the proliferative status of uterine epithelial cells was assessed following ovariectomy. Increased uterine epithelial cell proliferation was also revealed in ovariectomized Tgfbr1 Amhr2-Cre conditional knockout mice. We further demonstrated that transcript levels for fibroblast growth factor 10 (Fgf10) were markedly up-regulated in Tgfbr1 Amhr2-Cre conditional knockout uteri. Consistently, treatment of primary uterine stromal cells with TGF-beta 1 significantly reduced Fgf10 mRNA expression. Thus, our findings suggest a potential involvement of TGFBR1-mediated signaling in the regulation of uterine epithelial cell proliferation, and provide genetic evidence supporting the role of uterine epithelial cell proliferation in the pathogenesis of endometrial hyperplasia.