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

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.