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MicroRNA-195-5p Attenuates Pregnancy-Induced Hypertension by Inhibiting Oxidative Stress via OTX1/MAPK Signaling Pathway

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Abstract

Pregnancy-induced hypertension (PIH) is a hypertensive disorder during pregnancy and can induce perinatal death of human infants. MicroRNA (miR)-195-5p was validated to display low expression in severe preeclampsia placentas, but the role of miR-195-5p in pregnancy-induced hypertension (PIH) has not been investigated. The study emphasized on the functions and mechanism of miR-195-5p in PIH. A reduced uterine perfusion pressure (RUPP) rat model was established to mimic PIH in vivo. Adenovirus (Ad)-miR-195-5p agomir and/or Ad-OTX1 were further injected into some model rats. RT-qPCR was conducted to assess the expression of miR-195-5p and orthodenticle homeobox 1 (OTX1) in rat placental tissues, the isolated aortic endothelial cells (AECs), and in serum samples of PIH patients. Western blot analysis was implemented to measure the protein levels of OTX1, VEGFA, and key factors involved in the MAPK signaling pathway. The concentrations of oxidative stress markers (superoxide dismutase, catalase, and lipid hydroperoxide) in AECs and placental tissues of RUPP rats were measured by corresponding kits. The binding relation between miR-195-5p and OTX1 was verified using the dual-luciferase reporter assay. Hematoxylin–eosin staining was conducted to evaluate the pathological features of rat placental tissues. MiR-195-5p was downregulated, while OTX1 was upregulated in rat placental tissues and human serum samples of PIH patients. MiR-195-5p could target OTX1 and inversely regulate OTX1 expression in AECs and rat placental tissues. In addition, miR-195-5p can negatively regulate VEGFA level. Furthermore, miR-195-5p inactivates oxidative stress and the MAPK signaling by downregulating OTX1 in AECs. In vivo experiments revealed that OTX1 overexpression reversed the protective effect of miR-195-5p overexpression on placental damage and oxidative stress. MiR-195-5p alleviates PIH by inhibiting oxidative stress via targeting OTX1 and inactivating MAPK signaling.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors appreciate all the participants providing supports for this study.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Lili Liu and Chunfeng Yao have contributed equally to this work.

Authors and Affiliations

  1. Hospital Infection Management Division, Maternal and Child Health Hospital of Tangshan, Tangshan, 063000, China

    Lili Liu

  2. Department of Obstetrics Gynecology, Tangshan Workers’ Hospital, Tangshan, 063000, China

    Chunfeng Yao

  3. Department of Gynecology and Obstetrics, Maternal and Child Health Hospital of Tangshan, No. 1 Hetai Road, Lunan District, Tangshan, 063000, China

    Zhihui Song

Authors
  1. Lili Liu
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  2. Chunfeng Yao
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Contributions

LL and CY were the main designers of this study. LL, CY, and ZS performed the experiments and analyzed the data. LL, CY, and ZS drafted the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhihui Song.

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The authors declare no competing interests.

Ethical Approval

The Ethics Committee of Maternal and Child Health Hospital of Tangshan approved our study protocols. Animal studies were performed with strictness as per the guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health.

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Liu, L., Yao, C. & Song, Z. MicroRNA-195-5p Attenuates Pregnancy-Induced Hypertension by Inhibiting Oxidative Stress via OTX1/MAPK Signaling Pathway. Biochem Genet (2024). https://doi.org/10.1007/s10528-023-10612-5

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