Red Light Mitigates the Deteriorating Placental Extracellular Matrix in Late Onset of Preeclampsia and Improves the Trophoblast Behavior.

Red Light Mitigates the Deteriorating Placental Extracellular Matrix in Late Onset of Preeclampsia and Improves the Trophoblast Behavior.
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DOI:
10.1155/2022/3922368
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发表时间:
2022
影响因子:
3.2
通讯作者:
Weihrauch, Dorothee
Weihrauch, Dorothee
中科院分区:
其他
文献类型:
--
作者:
Griffin, Jakara;Krolikowski, John G.;Kounga, Kenisha;Struve, Janine;Keszler, Agnes;Lindemer, Brian;Bordas, Michelle;Broeckel, Grant;Lohr, Nicole L.;Weihrauch, Dorothee

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先兆子痫是一种严重的妊娠期疾病,在极端情况下可能导致母亲和胎儿损伤或死亡。增加氧化应激的既存疾病,例如,高血压和糖尿病,增加母亲患先兆子痫的风险。以前,我们确定当细胞外基质暴露于氧化应激时,滋养层功能受损,这可能导致胎盘形成不当。我们研究了氧化性ECM如何在先兆子痫中改变孕早期绒毛外滋养细胞的行为。我们证明了子痫前期ECM中晚期糖基化终产物(AGE)和脂质氧化终产物4-羟基壬烯醛水平升高(分别比对照组增加28%和32%),同时3-氯酪氨酸和3-硝基酪氨酸分别比对照组增加35%和82%。此外,我们假设,670 nm的光疗,具有抗氧化特性,逆转所观察到的滋养层功能障碍,如在改善迁移和减少细胞凋亡。由于NO对胎盘形成至关重要,我们检查了先兆子痫胎盘与健康胎盘的eNOS活性,没有发现差异;然而,670 nm光治疗可能通过使用替代NO来源引发了NO可用性增强。光暴露减少细胞凋亡和恢复滋养细胞迁移的水平在滋养细胞培养先兆子痫ECM。此外,670 nm照射使转化生长因子(TGFβ)和胎盘生长因子(PLGF)的表达恢复到在健康胎盘ECM上培养的滋养层中观察到的水平。我们的结论是,670 nm光的应用可以成功地减轻晚发型先兆子痫受损的胎盘微环境所描述的恢复滋养细胞的行为。
Preeclampsia is a serious pregnancy disorder which in extreme cases may lead to maternal and fetal injury or death. Preexisting conditions which increase oxidative stress, e.g., hypertension and diabetes, increase the mother's risk to develop preeclampsia. Previously, we established that when the extracellular matrix is exposed to oxidative stress, trophoblast function is impaired, and this may lead to improper placentation. We investigated how the oxidative ECM present in preeclampsia alters the behavior of first trimester extravillous trophoblasts. We demonstrate elevated levels of advanced glycation end products (AGE) and lipid oxidation end product 4-hydroxynonenal in preeclamptic ECM (28%, and 32% increase vs control, respectively) accompanied with 35% and 82% more 3-chlorotyrosine and 3-nitrotyrosine vs control, respectively. Furthermore, we hypothesized that 670 nm phototherapy, which has antioxidant properties, reverses the observed trophoblast dysfunction as depicted in the improved migration and reduction in apoptosis. Since NO is critical for placentation, we examined eNOS activity in preeclamptic placentas compared to healthy ones and found no differences; however, 670 nm light treatment triggered enhanced NO availability presumably by using alternative NO sources. Light exposure decreased apoptosis and restored trophoblast migration to levels in trophoblasts cultured on preeclamptic ECM. Moreover, 670 nm irradiation restored expression of Transforming Growth Factor (TGFβ) and Placental Growth Factor (PLGF) to levels observed in trophoblasts cultured on healthy placental ECM. We conclude the application of 670 nm light can successfully mitigate the damaged placental microenvironment of late onset preeclampsia as depicted by the restored trophoblast behavior.
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