Exosomal MicroRNA-23-5p Derived from Bone Marrow Mesenchymal Stem Cells Relieves Inflammatory Response in Rheumatoid Arthritis

We aimed to explore the mechanism underlying microRNA-23-5p from exosomes (exo-miR-23-5p) of BMSCs in rheumatoid arthritis (RA). The candidate related genes of miR-23-5p were screened in RA by bioinformatics analysis through gain- and loss-function method along with analysis of histopathological changes in mice and RAC2 expression as well as the level of pro-inflammatory factors. In vivo RA model was established to detect miR-23-5p’s effect on RA. miR-23-5p level was significantly reduced in RA cells and RAC2 was highly expressed. Expression of RAC2 was inhibited and targeted by miR-23-5p in RA. Exo-miR-23-5p treatment effectively alleviated joint destruction, reduced inflammatory factor secretion in tissues and serum, as well as decreased RAC2 expression in RA model. In conclusion, the miR-23-5p in the BMSC-exo delays the inflammatory response in RA, indicating that it might be a new target for treating RA.

Exosomal MicroRNA-325 Enhances Trophoblast Migration and Invasion Through Downregulation of Lethal-7b and Upregulation of Forkhead Box Protein O1 Expression in Preeclampsia

We aimed to explore the mechanism by how microRNA (miRNA)-325 derived from marrow mesenchymal stem cell exosomes (MSC-exos) affects the trophoblast progression in preeclampsia (PE). RT-qPCR detected the level of miRNA let-7b and FOXO1 in the placenta tissue of PE patients. Functional experiment was performed to analyze the effect of FOXO1 inhibitor and let-7b mimics on cell migration, invasion and apoptosis through Transwell assay and TUNEL staining. The trophoblast cell was co-cultured with overexpressed-miR-325 MSC-exos to measure gene expression and cell progression. let-7b was highly and FOXO1 was lowly expressed in PE placenta tissue. let-7b directly targeted and inhibited FOXO1 expression. Importantly, as miR-325 was internalized by trophoblast cells through MSC-exos, MSC-exos overexpressing miR-325 inhibited let-7b expression in trophoblasts, up-regulated FOXO1 and activated AKT signaling pathway. Further, MSC-exos treatment promoted invasion and migration of trophoblast cell and inhibited apoptosis. In conclusion, miR-325 derived from MSC-exos promotes the invasion and migration of trophoblast cells in PE through inhibition of let7b and upregulation of FOXO1.