HB-EGF Ameliorates Oxidative Stress-Mediated Uterine Decidualization Damage
HB-EGF Ameliorates Oxidative Stress-Mediated Uterine Decidualization Damage
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DOI：
10.1155/2019/6170936
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发表时间：
2019-12
影响因子：
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通讯作者：
Hai-Fan Yu;Cui-Cui Duan-Cui;Zhan‐Qing Yang;Yu‐Si Wang;Z. Yue;B. Guo
中科院分区：
文献类型：
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作者：
Hai-Fan Yu;Cui-Cui Duan-Cui;Zhan‐Qing Yang;Yu‐Si Wang;Z. Yue;B. Guo
HB-EGF是子宫蜕膜形成所必需的，但其抗氧化功能仍不清楚。在此，我们发现HB-EGF促进了间质细胞的增殖，加速了细胞周期从G1期向S期的转变，并增强了蜕膜形成过程中已建立的子宫基质细胞分化标志物Pr18a2、Pr13c1和ALP的表达或活性。在氧化应激条件下，间质细胞分化受损，但rHB-EGF可消除这种损害，并伴有氧化应激生物标志物ROS和MDA水平的降低，表明HB-EGF具有抗氧化作用。进一步的分析表明，HB-EGF增强了抗氧化酶SOD、CAT和GPx的活性，而加入GPx抑制剂MS则减弱了RHB-EGF对Pr18a2、Pr13c1和ALP的诱导。同时，HB-EGF可使H_2O_2暴露后GSH含量减少，GSH/GSSG比值恢复，但对NOx活性无明显影响。外源性rHB-EGF可改善氧化应激对线粒体DNA拷贝数、ATP水平、线粒体膜电位以及线粒体呼吸链复合体I和III活性的损伤，同时降低线粒体超氧化物歧化水平，其活性被ROT和AA阻断，导致rHB-EGF不能保护基质细胞分化免受损伤。此外，HB-EGF通过抑制Caspase-3活性和Bax的表达，恢复Bcl2的表达水平，从而阻止间质细胞的凋亡。总之，HB-EGF可能改善氧化应激介导的子宫蜕膜损伤。
HB-EGF is essential for uterine decidualization, but its antioxidant function remains largely unclear. Here, we found that HB-EGF promoted the proliferation of stromal cells followed by the accelerated transition of the cell cycle from G1 to S phase and enhanced the expression or activity of Prl8a2, Prl3c1, and ALP which were well-established markers for uterine stromal cell differentiation during decidualization. Under oxidative stress, stromal cell differentiation was impaired, but this impairment was abrogated by rHB-EGF accompanied with the reduced levels of ROS and MDA which were regarded as the biomarkers for oxidative stress, indicating an antioxidant role of HB-EGF. Further analysis revealed that HB-EGF enhanced the activities of antioxidant enzymes SOD, CAT, and GPX, where addition of GPX inhibitor MS attenuated the induction of rHB-EGF on Prl8a2, Prl3c1, and ALP. Meanwhile, HB-EGF rescued the content of GSH and restored the ratio of GSH/GSSG after exposure to H2O2 but did not alter NOX activity. Along with a decline for mitochondrial superoxide, exogenous rHB-EGF improved the damage of oxidative stress on mtDNA copy number, ATP level, mitochondrial membrane potential, and activities of mitochondrial respiratory chain complex I and III whose blockage by ROT and AA led to a failure of rHB-EGF in protecting stromal cell differentiation against injury. Moreover, HB-EGF prevented stromal cell apoptosis by inhibiting Caspase-3 activity and Bax expression and recovering the level of Bcl-2 mRNA. Collectively, HB-EGF might ameliorate oxidative stress-mediated uterine decidualization damage.