BMSCs Downregulate CXCL12 by Secreting Exosomal miR-20a-5p to Promote Macrophage M2 Polarization and Alleviate the Development of Sepsis.

Abstract

Objective: Sepsis is a syndrome of the systemic inflammatory response caused by infection that can endanger a patient's life. The aim of this study was to explore the molecular mechanism by which bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exo) carrying miR-20a-5p regulate the progression of sepsis.

Methods: Clinical samples from sepsis patients were collected. Mouse and cell models of sepsis were induced by lipopolysaccharide (LPS). The levels of related genes and proteins were determined by RT‒qPCR, Western blotting and ELISA. CCK-8 and flow cytometry assays were used to assess cell viability, apoptosis, and markers of macrophage polarization.

Results: In septic patients, miR-20a-5p levels were significantly lower and CXCL12 expression was significantly increased. After LPS induction, M2 polarization of macrophages was significantly reduced, the level of inflammatory factors was increased, and apoptosis was increased. The addition of BMSCs-exo increased the miR-20a-5p level and decreased the expression of CXCL12 in macrophages, thereby promoting macrophage M2 polarization and reducing the levels of inflammatory factors.

Conclusion: This study demonstrated for the first time that BMSCs-exo promoted the polarization of M2 macrophages through the miR-20a-5p/CXCL12 axis, thus alleviating the development of sepsis. These findings provide a new theoretical basis for the targeted treatment of sepsis with exosomes or miR-20a-5p.