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MiR-124-3p reduces angiotensin II-dependent hypertension by down-regulating EGR1

Journal of Human Hypertension volume 35, pages 696–708 (2021)Cite this article

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Abstract

Through previous literature studies, we found that miR-124-3p may be associated with hypertension. Therefore, we investigated the relationship between miR-124-3p and hypertension in Human Umbilical Vein Endothelial Cells (HUVECs) induced by angiotensin II (AngII). AngII-induced HUVECs model was constructed and the expression of miR-124-3p was detected by qRT-PCR. After transfected cells, apoptosis and ROS production were detected by flow cytometry, caspase-3 kit, and DCFH-DA staining. The target genes of miR-124-3p were predicted and verified by TargrtScan, Luciferase assay, qRT-PCR, and western blot. After silencing Early growth response factor 1 (siEGR1), its effects on apoptosis and ROS production were explored. Finally, the rescue experiments were conducted to explore the mechanism of miR-124-3p to reduce hypertension. MiR-124-3p was underexpressed in the cell model. In Ang II-induced HUVECs, the number of apoptosis increased, the content of caspase-3 was higher, and ROS production increased. However, these effects could be partially inhibited by miR-124-3p mimic. EGR1 was down-regulated by miR-124-3p, and siEGR1 was able to inhibit apoptosis and ROS production of cell model. In the final rescue experiments, miR-124-3p partially reversed the effect of Ang-II on the viability, migration, invasion and apoptosis and ROS production in HUVECs by down-regulating EGR1. MiR-124-3p inhibits Ang II-induced apoptosis and ROS production in HUVECs by down-regulating EGR1.

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Fig. 1: MiR-124-3p mimic inhibits the promoting effect of angiotensin II (AngII) on apoptosis in HUVECs.
Fig. 2: MiR-124-3p mimic inhibits the effect of AngII on Caspase-3 expression and reactive oxygen species (ROS) production in HUVECs.
Fig. 3: MiR-124-3p can down-regulate the expression of Early growth response factor 1 (EGR1).
Fig. 4: Silencing EGR1 (siEGR1) can inhibits the promoting effect of AngII on apoptosis in HUVECs.
Fig. 5: SiEGR1 can inhibits the effect of AngII on Caspase-3 expression and ROS production in HUVECs.
Fig. 6: MiR-124-3p partially reversed the promoting effect of AngII on apoptosis in HUVECs by down-regulating EGR1.
Fig. 7: MiR-124-3p partially reversed the effect of AngII on Caspase-3 expression and ROS production in HUVECs by down-regulating EGR1.
Fig. 8: MiR-124-3p partially reversed the inhibitory effect of AngII on viability, migration, and invasion in HUVECs by down-regulating EGR1.

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Funding

This work was supported by the Lishui public welfare Technology Application Research Project [2019GYX28]; the Zhejiang basic public welfare research plan [LGF19H02008].

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  1. These authors contributed equally: Lingchun Lv, Jiayi Shen

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Lishui Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Lingchun Lv, Jiayi Shen, Jian Xu, Xiaoyan Wu, Chunlai Zeng, Li Lin & Tiemin Wei

  2. The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China

    Lingchun Lv

  3. Lishui Cardiovascular Clinical Research Center, Zhejiang Chinese Medical University, Hangzhou, China

    Jiayi Shen & Chunlai Zeng

  4. Department of Cardiovascular Medicine, Zhejiang Traditional Chinese Medicine Hospital, Hangzhou, China

    Wei Mao

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Lv, L., Shen, J., Xu, J. et al. MiR-124-3p reduces angiotensin II-dependent hypertension by down-regulating EGR1. J Hum Hypertens 35, 696–708 (2021). https://doi.org/10.1038/s41371-020-0381-x

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