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Exosomal microRNA-342-5p from human umbilical cord mesenchymal stem cells inhibits preeclampsia in rats

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Abstract

We aimed to investigate the inhibitory effect of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes (hucMSC-Exos) transmitting microRNA-342-5p (miR-342-5p) on the development of preeclampsia (PE) by targeting programmed cell death 4 (PDCD4). The primary hucMSCs were cultured and transfected with miR-342-5p, and the exosomes (Exo) were extracted from the hucMSCs. PE rats were performed with an intraperitoneal injection of L-NAME from days 11 to 19 of gestation, and injection of Exo, Exo-negative control (NC), Exo-miR-342-5p agomir, Exo-miR-342-5p antagomir, and overexpressing PDCD4 (oe-PDCD4) vector into the placenta on the 16th day of pregnancy. HE staining was utilized to observe the pathological changes in placental tissues. TUNEL staining was implemented to evaluate cell apoptosis in placental tissues. Blood pressure and 24-h urinary protein in pregnant rats were measured by a non-invasive rat tail artery blood pressure measurement and protein auto-analyzer. Expressions of miR-342-5p, PDCD4, proinflammatory cytokines (TNF-α and IL-1β), and anti-inflammatory cytokines (IL-10 and TGF-β) were detected by RT-qPCR, and PDCD4 protein expression was determined by Western blot. The interaction between miR-342-5p and PDCD4 was analyzed by luciferase activity assay. MiR-342-5p was downregulated while PDCD4 was upregulated in the placental tissues of PE rats. HucMSC-Exo relieved pathology and suppressed inflammatory response, and apoptosis in the placental tissues, as well as reducing blood pressure and 24-h urinary protein of PE rats. Elevated miR-342-5p enhanced the promoting influence of hucMSC-Exo on PE rats, while inhibited miR-342-5p reversed the functions of hucMSC-Exo on PE rats. miR-342-5p targeted PDCD4. Overexpression of PDCD4 worsened the development of PE in rats. HucMSC-Exo conveying elevated miR-342-5p inhibits the development of PE in a rat model through downregulating PDCD4.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the study on the correlation between early spontaneous abortion and villus chromosome abnormality [grant number 2014C312068].

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Hb.R. contributed to study design; Y.C. contributed to manuscript editing; Jx.J. and Xp.C. contributed to experimental studies; J.X. and Lh.A. contributed to data analysis.

All authors read and approved the final manuscript.

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Correspondence to Haibo Ruan.

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Written informed consent was acquired from all patients before this study. Animal experiments were accorded with the Guide to the Management and Use of Laboratory Animals issued by the National Institutes of Health. The protocol of this study was approved by the Ethics Committee of the First People’s Hospital of WenLing ZheJiang and based on the ethical principles of the Helsinki Declaration. The protocol of animal experiments was approved by the Institutional Animal Care and Use Committee of the First People’s Hospital of WenLing ZheJiang.

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Chen, Y., Jin, J., Chen, X. et al. Exosomal microRNA-342-5p from human umbilical cord mesenchymal stem cells inhibits preeclampsia in rats. Funct Integr Genomics 23, 27 (2023). https://doi.org/10.1007/s10142-022-00931-y

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  • DOI: https://doi.org/10.1007/s10142-022-00931-y

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