Effects of birth trauma and estrogen on urethral elastic fibers and elastin expression.
Effects of birth trauma and estrogen on urethral elastic fibers and elastin expression.
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DOI：
10.1016/j.urology.2010.02.055
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发表时间：
2010-10
期刊：
影响因子：
2.1
通讯作者：
Lin CS
中科院分区：
文献类型：
--
作者：
Lin G;Ning H;Wang G;Banie L;Lue TF;Lin CS
为探讨产伤和雌激素对大鼠尿道弹性纤维和弹性蛋白表达的影响，将孕鼠分为假手术组（仅分娩）、DVDO组（分娩、阴道扩张和卵巢切除）和DVDO+E2组（雌激素）。分别于术后2、4、8、12周取材，行弹性纤维染色和RT-PCR分析。用TGF-β1和/或雌激素处理尿道细胞，并分析弹性蛋白mRNA表达。同时检测尿道细胞中Smad 1和Smad 3/4反应元件对TGF-β1和雌激素的反应活性。在治疗后8周，与仅递送大鼠相比，DVDO大鼠的尿道具有更少且更短的弹性纤维，并且与DVDO大鼠相比，DVDO+E2大鼠的尿道具有更少且更短的弹性纤维。弹性蛋白mRNA在仅递送大鼠中以低水平表达，并且在第2、4和8周时在DVDO大鼠中以越来越高的水平表达，但是与第8周时的DVDO大鼠相比，在DVDO+E2大鼠中以急剧降低的水平表达。当TGF-β1浓度增加到1 ng/ml时，尿道细胞表达的弹性蛋白mRNA水平逐渐升高。在此TGF-β1浓度下，在TGF-β1处理之前或之后用雌激素处理时，尿道细胞表达的弹性蛋白mRNA水平显著降低。TGF-β1可激活Smad 1和Smad 3/4反应元件，雌激素可抑制这种激活。出生创伤似乎通过TGF-β1信号传导激活尿道弹性蛋白表达。雌激素干扰这种信号传导，导致弹性纤维的不正确组装。
To investigate the effects of birth trauma and estrogen on urethral elastic fibers and elastin expression Pregnant rats were subjected to sham operation (Delivery-only), DVDO (delivery, vaginl distension and ovariectomy), or DVDO+E2 (estrogen). At 2, 4, 8, or 12 weeks, their urethras were harvested for elastic fiber staining and RT-PCR analysis. Urethral cells were treated with TGF-β1 and/or estrogen and analyzed for elastin mRNA expression. Urethral cells were also examined for the activities of Smad1 and Smad3/4 responsive elements in response to TGF-β1 and estrogen. At 8 weeks post-treatment, the urethras of DVDO rats had fewer and shorter elastic fibers when compared to Delivery-only rats, and those of DVDO+E2 rats had fewer and shorter elastic fibers when compared to DVDO rats. Elastin mRNA was expressed at low levels in Delivery-only rats and at increasingly higher levels in DVDO rats at 2, 4, and 8 weeks but at sharply lower levels in DVDO+E2 rats when compared to DVDO rats at 8 weeks. Urethral cells expressed increasingly higher levels of elastin mRNA in response to increasing concentrations of TGF-β1 up to 1 ng/ml. At this TGF-β1 concentration, urethral cells expressed significantly lower levels of elastin mRNA when treated with estrogen prior to or after TGF-β1 treatment. Both Smad1 and Smad3/4 responsive elements were activated by TGF-β1 and such activation was suppressed by estrogen. Birth trauma appears to activate urethral elastin expression via TGF-β1 signaling. Estrogen interferes with this signaling, resulting in improper assembly of elastic fibers.
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