Activation of the MAPK/ERK Cell-Signaling Pathway in Uterine Smooth Muscle Cells of Women With Adenomyosis
Activation of the MAPK/ERK Cell-Signaling Pathway in Uterine Smooth Muscle Cells of Women With Adenomyosis
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DOI：
10.1177/1933719115589410
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发表时间：
2015-12-01
影响因子：
2.9
通讯作者：
Batteux, Frederic
中科院分区：
文献类型：
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作者：
Streuli, Isabelle;Santulli, Pietro;Batteux, Frederic
我们研究了子宫腺肌病患者的子宫肌层是否有本质上的不同。我们研究了丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPKs/ERK）和磷酸肌醇3-激酶/雷帕霉素的哺乳动物靶蛋白/AKT（PI 3 K/mTOR/AKT）细胞信号传导通路，与子宫内膜异位症的发病机制有关，也可能在子宫腺肌病妇女的子宫平滑肌细胞（uSMC）中被激活，并测量活性氧（ROS）的产生，在子宫内膜异位症中，促炎介质调节细胞增殖并已显示激活MAPK/ERK通路。uSMC培养物来源于子宫腺肌病患者和对照组子宫肌瘤患者子宫切除术或肌瘤切除术期间获得的子宫肌层活检。与对照组相比，子宫腺肌病患者uSMC的增殖和MAPK/ERK细胞信号通路的体外激活增加。PI 3 K/mTOR/AKT通路的激活不显著。ROS的产生和ROS解毒途径在子宫腺肌病患者和对照组的uSMC之间没有差异，这表明MAPK/ERK途径的ROS非依赖性激活。我们的研究结果还提供了蛋白激酶抑制剂和雷帕霉素可以控制uSMC在体外的增殖的证据，这表明MAPK/ERK和PI 3 K/mTOR/AKT通路在子宫腺肌病和平滑肌瘤妇女的uSMC的增殖中的意义。
We investigated whether the myometrium might be intrinsically different in women with adenomyosis. We studied whether the mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPKs/ERKs) and phosphoinositide 3-kinase/mammalian target of rapamycin/AKT (PI3K/mTOR/AKT) cell-signaling pathways, implicated in the pathogenesis of endometriosis, might also be activated in uterine smooth muscle cells (uSMCs) of women with adenomyosis and measured the production of reactive oxygen species (ROS), proinflammatory mediators that modulate cell proliferation and have been shown to activate the MAPK/ERK pathway in endometriosis. The uSMC cultures were derived from myometrium biopsies obtained during hysterectomy or myomectomy in women with adenomyosis and controls with leiomyoma. Proliferation of uSMCs and in vitro activation of the MAPK/ERK cell-signaling pathway were increased in women with adenomyosis compared to controls. The activation of the PI3K/mTOR/AKT pathway was not significant. The ROS production and ROS detoxification pathways were not different between uSMCs of women with adenomyosis and controls suggesting an ROS-independent activation of the MAPK/ERK pathway. Our results also provide evidence that protein kinase inhibitors and the rapanalogue temsirolimus can control proliferation of uSMCs in vitro suggesting an implication of the MAPK/ERK and the PI3K/mTOR/AKT pathways in proliferation of uSMCs in women with adenomyosis and leiomyomas.