Smad signaling coincides with epithelial-mesenchymal transition in a rat model of intrauterine adhesion
Smad signaling coincides with epithelial-mesenchymal transition in a rat model of intrauterine adhesion
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Smad 信号传导与大鼠宫腔粘连模型中的上皮间质转化一致
DOI：
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Long Sui
中科院分区：
文献类型：
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作者：
Luo-Pei Guo;Li-Mei Chen;Fang Chen;Ning-Hong Jiang;Long Sui
目的：子宫内粘连（IUA）是一种主要由组织损伤引起的纤维化疾病，其发生机制尚不清楚。本研究的目的是探讨TGF-β1/BMP 7/Smad信号传导在子宫内膜异位症中与上皮-间充质转化（EMT）同时发生的作用。方法：24只雌性SD大鼠随机分为IUA组和假手术组。对于每只动物，对左侧子宫（IUA-L，Sham-L）进行机械损伤或假手术，右侧子宫（IUA-R，Sham-R）用作对照。在第7天和第28天分批处死动物。观察子宫内膜形态、腺体数量、微血管密度（MVD）、子宫内膜纤维化面积、EMT标志物免疫组化（IHC）、TGF-β1、磷酸化Smad 3（pSmad 3）、BMP 7、磷酸化Smad 1/5（pSmad 1/5）和雌激素受体（ER）的表达。此外，还分析了这些IHC标记之间的相关性。RT-PCR和Western blot检测相关基因。结果：与其他各组相比，IUA-L组腺体数量和MVD明显减少。间质纤维化率和aSMA水平也明显升高。IUA-L组TGF-β1和pSmad 3表达水平持续升高，而BMP 7、pSmad 1/5和ER表达水平较低。EMT标志物E-cadherin减少，而N-cadherin增加。假手术组和对照组在这些标志物上没有显着差异。IUA-L组E-cadherin与a-SMA、纤维化率与BMP 7、TGF-β1与pSmad 3、BMP 7与pSmad 1/5相关，均具有统计学意义。7 d IUA-L组TGF-β1、α-SMA、ccn 2 mRNA表达高于7 d IUA-R组，BMP 7 mRNA表达低于7 d IUA-R组，差异有统计学意义。7 d IUA-L组BMP 7蛋白表达低于7 d IUA-R组，差异有统计学意义。结论：这些结果表明，Smad信号与EMT在子宫内膜纤维化的发展中的潜在作用。
Purpose: Intrauterine adhesion (IUA) is a fibrotic disease mainly caused by tissue injury, yet the mechanism is poorly understood. The aim of this study was to investigate the roles of TGF-β1/BMP7/Smad signaling coincident with epithelial-mesenchymal transition (EMT) in IUA. Methods: Twenty-four female SD rats were divided into IUA and sham groups. For each animal, a mechanical injury or sham operation was performed on the left uterus (IUA-L, Sham-L), and the right uterus (IUA-R, Sham-R) was used as the control. Animals were sacrificed in batches on days 7 and 28. The endometrial morphology, number of endometrial glands, microvascular density (MVD), area of endometrial fibrosis and immunohistochemistry (IHC) analysis of biomarkers of EMT, as well as levels of TGF-β1, phosphorylated Smad3 (pSmad3), BMP7, phosphorylated Smad1/5 (pSmad1/5) and estrogen receptor (ER) were evaluated. Besides, the correlation between these IHC markers was also analyzed. RT-PCR and western blot were used to test relevant genes. Results: Compared with other groups, the IUA-L group showed a significant decrease in the number of glands and MVD. And it also showed a significant increase in the stromal fibrosis rate and aSMA level. Moreover, in the IUA-L group, TGF-β1 and pSmad3 levels were consistently high, and levels of BMP7, pSmad1/5 and ER were low. EMT markers E-cadherin was decreased, while N-cadherin was increased. Sham and control groups showed no significant difference in these markers. In addition, E-cadherin with a-SMA, fibrosis rate with BMP7, TGF-β1 with pSmad3 and BMP7 with pSmad1/5 showed correlation in IUA-L group, which had statistical .significance. The mRNA expression of TGF-β1, a-SMA and ccn2 in 7 d IUA-L was higher than 7 d IUA-R while BMP7 was lower, which had significant difference. The protein expression of BMP7 in 7 d IUA-L was lower than 7 d IUA-R, which had significant difference. Conclusions: These results suggest a potential role of Smad signaling together with EMT in endometrial fibrosis development.