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金丝桃苷通过激活复发性自然流产中HTR-8/SVneo滋养层细胞的JAK1/STAT3信号通路促进其增殖、迁移和侵袭。

Hyperin promotes proliferation, migration, and invasion of HTR-8/SVneo trophoblast cells via activation of JAK1/STAT3 pathway in recurrent spontaneous abortions.

作者信息

Mu Zhenni, Shen Sinan, Tang Li, Liu Yingdie, Zhou Ziwei, Lei Lei

机构信息

College of Integrated Traditional and Western Medicine, Hunan University of Chinese Medicine, Changsha, China.

The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China.

出版信息

Heliyon. 2023 Jan 13;9(1):e12958. doi: 10.1016/j.heliyon.2023.e12958. eCollection 2023 Jan.

DOI:10.1016/j.heliyon.2023.e12958
PMID:36747955
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9898646/
Abstract

The proliferation of extravillous trophoblasts (EVT) and their further migration, invasion, and differentiation into the decidual and myometrial vasculature are vital for spiral artery remodeling. These physiological functions of EVT are also essential steps in the implantation of the human embryo and the formation of the placenta and are closely related to pregnancy maintenance and the occurrence of abortion. Hyperin is a flavonoid with anti-inflammatory, pro-proliferative, and anti-apoptotic properties. Consequently, we investigated the previously unexplored effects of hyperin on the proliferation, migration, and invasion of HTR-8/SVneo cells. Human extravillous trophoblast-derived HTR-8/SVneo cells were incubated with different concentrations of hyperin (0, 5, 10, 25, 50, and 100 μM) to observe the changes in cell proliferation, migration, invasive capacity, and pathway activation. Proliferation, migration, and invasion were promoted by activating the JAK1/STAT3 pathway in HTR-8/SVneo cells treated with hyperin. In addition, brepocitinib (PF-06700841) significantly inhibited the proliferation, migration, and invasion effects of hyperin on HTR-8/SVneo cells. experiments confirmed that hyperin reduces the embryo loss rate in recurrent spontaneous abortion (RSA) model mice. Furthermore, our study revealed that hyperin promoted the proliferation, migration, and invasion of HTR-8/SVneo cells via activation of the JAK1/STAT3 pathway, further improving pregnancy outcomes in RSA.

摘要

绒毛外滋养层细胞(EVT)的增殖及其进一步迁移、侵袭并分化为蜕膜和子宫肌层血管,对于螺旋动脉重塑至关重要。EVT的这些生理功能也是人类胚胎着床、胎盘形成的关键步骤,与妊娠维持及流产的发生密切相关。金丝桃苷是一种具有抗炎、促增殖和抗凋亡特性的黄酮类化合物。因此,我们研究了金丝桃苷对HTR-8/SVneo细胞增殖、迁移和侵袭的影响,此前尚未有相关探索。将人绒毛外滋养层来源的HTR-8/SVneo细胞与不同浓度的金丝桃苷(0、5、10、25、50和100 μM)孵育,以观察细胞增殖、迁移、侵袭能力及信号通路激活的变化。金丝桃苷处理的HTR-8/SVneo细胞通过激活JAK1/STAT3信号通路促进了细胞的增殖、迁移和侵袭。此外,巴瑞替尼(PF-06700841)显著抑制了金丝桃苷对HTR-8/SVneo细胞的增殖、迁移和侵袭作用。实验证实,金丝桃苷降低了复发性自然流产(RSA)模型小鼠的胚胎丢失率。此外,我们的研究表明,金丝桃苷通过激活JAK1/STAT3信号通路促进了HTR-8/SVneo细胞的增殖、迁移和侵袭,进一步改善了RSA的妊娠结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c265/9898646/ff367bc2c927/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c265/9898646/b11392eb0583/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c265/9898646/8475d7bdee14/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c265/9898646/2b3db9c0cf62/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c265/9898646/8ccc3640b00d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c265/9898646/e2127d5c3482/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c265/9898646/ff367bc2c927/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c265/9898646/b11392eb0583/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c265/9898646/8475d7bdee14/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c265/9898646/2b3db9c0cf62/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c265/9898646/8ccc3640b00d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c265/9898646/e2127d5c3482/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c265/9898646/ff367bc2c927/gr6.jpg

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本文引用的文献

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[Hyperoside protects mouse spermatocytes GC-2 cells from oxidative damage by activating the Keap1/Nrf2/HO-1 pathway].[金丝桃苷通过激活Keap1/Nrf2/HO-1信号通路保护小鼠精母细胞GC-2细胞免受氧化损伤]
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Recent Advances in Treatment of Recurrent Spontaneous Abortion.复发性自然流产的治疗新进展。
Obstet Gynecol Surv. 2022 Jun;77(6):355-366. doi: 10.1097/OGX.0000000000001033.
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Hyperoside: A review on its sources, biological activities, and molecular mechanisms.
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Phytother Res. 2022 Jul;36(7):2779-2802. doi: 10.1002/ptr.7478. Epub 2022 May 13.
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Hyperoside suppresses osteoclasts differentiation and function through downregulating TRAF6/p38 MAPK signaling pathway.金丝桃苷通过下调TRAF6/p38丝裂原活化蛋白激酶信号通路抑制破骨细胞的分化和功能。
J Asian Nat Prod Res. 2022 Dec;24(12):1157-1168. doi: 10.1080/10286020.2022.2056028. Epub 2022 Apr 18.
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