Expression and deoxyribonucleic acid-binding activity of the nuclear factor κB family in the human myometrium during pregnancy and labor
Expression and deoxyribonucleic acid-binding activity of the nuclear factor κB family in the human myometrium during pregnancy and labor
复制标题
DOI：
10.1210/jc.2004-0873
复制
发表时间：
2004-11-01
影响因子：
5.8
通讯作者：
Robson, SC
中科院分区：
文献类型：
--
作者：
Chapman, NR;Europe-Finner, GN;Robson, SC
在人类中，在分娩开始时，控制从肌层静止到协调收缩的因素还没有很好的定义。分娩的开始本身与一些促炎因子的增加有关，其中许多因子受核因子kappaB(NF-kappaB)转录因子家族的调节。检测妊娠和分娩过程中子宫肌层中核因子-kappaB的表达和DNA结合活性。与非妊娠(NP)对照组相比，妊娠子宫肌层中c-Rel、p50和p105核因子-kappaB的表达水平显著降低，而relA亚单位的表达保持一致。重要的是，在分娩期间，观察到所有子宫肌层样本中所有亚单位的表达相对于NP水平都显著降低。此外，对于relA、c-rel和p50亚单位，在劳作的子宫上段(子宫体部)和子宫下段肌层之间存在表达梯度。未检测到RelB或p52亚基。EMSA发现妊娠和分娩期间子宫肌层中的NF-kappaB亚基组成发生了变化，NP组织中的p50同源二聚体被妊娠和分娩样本中的relA：p50异源二聚体所取代。值得注意的是，RELA在丝氨酸-536处被磷酸化，这意味着磷脂酰肌醇-3-激酶/AKT通路参与了子宫肌层中核因子-kappaB的功能。
In humans, the factors that govern the switch from myometrial quiescence to coordinated contractions at the initiation of labor are not well defined. The onset of parturition is itself associated with increases in a number of proinflammatory factors, many of which are regulated by the nuclear factor kappaB (NF-kappaB) family of transcription factors. The expression and DNA-binding activity of NF-kappaB in the myometrium during gestation and parturition were examined. Levels of c-Rel, p50, and p105 NF-kappaB species were dramatically reduced in pregnant myometrium compared with nonpregnant (NP) controls, whereas expression of the RelA subunit remained uniform. Importantly, during labor, expression of all subunits was observed to be significantly reduced in all myometrial samples studied relative to NP levels. Moreover, for RelA, c-Rel, and p50 subunits, there was a gradient of expression between laboring upper ( corpus) and lower uterine segment myometrium. No RelB or p52 subunits could be detected. EMSAs identified changes in NF-kappaB subunit composition in the myometrium during pregnancy and labor, with p50 homodimers predominant in NP tissues being replaced with RelA: p50 heterodimers in pregnant and laboring samples. Significantly, RelA was observed to be phosphorylated at serine-536, implicating the involvement of the phosphatidylinositol-3-kinase/AKT pathway in NF-kappaB function in the myometrium.