Tumor-associated macrophage-derived exosomal microRNA-155-5p stimulates intracranial aneurysm formation and macrophage infiltration

Abstract

Abstract Tumor-associated macrophages (TAMs) play a regulatory role in inflammation and cancer. Exosomes derived from macrophages carrying microRNAs (miRNAs or miRs) are of great value for cancer therapy. Gremlin 1 (GREM1), a member of the antagonists of secreted bone morphogenetic protein, has been implicated in the pathophysiology of multiple diseases or cancers. Based on the predictions of miRNA–mRNA interaction, GREM1 was found to be a target gene of miR-155-5p. Here, the present study aims to explore the role of TAM-derived exosomal miR-155-5p by regulating GREM1 in intracranial aneurysm (IA). The collected results showed that GREM1 was down-regulated in IA, while miR-155-5p was up-regulated in TAM-derived exosomes. Smooth muscle cells (SMCs) were co-cultured with TAMs or exposed to exosomes derived from TAMs transfected with either miR-155-5p mimic or miR-155-5p inhibitor for exploring their roles in proliferation and migration of SMCs in vitro. Accordingly, in vitro experiments showed that TAM-derived exosomal miR-155-5p could promote proliferation and migration of SMCs by targeting GREM1. The effects of TAM-derived exosomal miR-155-5p on IA formation and TAM activation and infiltration by regulation of GREM1 in vivo were measured in IA rats injected with exosomes or those from TAMs transfected with miR-155-5p inhibitor. In vivo experimental results consistently confirmed that TAM-derived exosomes carrying miR-155-5p promoted IA formation and TAM activation and infiltration. In conclusion, TAM-derived exosomal miR-155-5p promotes IA formation via GREM1, which points to miR-155-5p as a possible therapeutic target for IA.