Exosomes from Adipose-Derived Stem Cells Promotes VEGF-C-Dependent Lymphangiogenesis by Regulating miRNA-132/TGF-β Pathway

Abstract

Background/Aims: Lymphangiogenesis plays an important role in the pathogenesis of inflammatory bowel diseases (IBD), and vascular endothelial growth factor-C (VEGF-C) is a powerful lymphangiogenic factor. Adipose-derived stem cells (ADSCs) are a promising therapeutic modality for several diseases because ADSCs secret growth factors and exosomes, which modulate hostile microenvironments affected by diseases. However, the effect of exosomes on VEGF-C-dependent lymphangiogenesis and its mechanism remain unclear. Methods: ADSCs were cultured in media with or without recombinant VEGF-C and exosomes were extracted from conditioned medium (CM). Lymphatic endothelial cells (LECs) were treated with ADSCs-derived exosomes, then proliferation, migration and tube formation of LECs were assayed using cell counting Kit-8 (CCK-8), transwell chamber inserts and matrigel-based tube formation assay respectively. Results: We identified significantly higher levels of miR-132 in exosomes isolated from VEGF-C-treated ADSCs (ADSCs/VEGF-C) than in those from ADSCs control. miR-132 was directly transferred from ADSCs to the LECs by the mediation of exosomes. The exosomes from ADSCs/VEGF-C promoted LECs proliferation, migration, and tube formation more potently than the exosomes from ADSCs, whereas pretreatment of ADSCs with miR-132 inhibitor attenuates VEGF-C-dependent lymphangiogenic response. Finally we reveal that miR-132 promotes lymphangiogenic response by directly targeting Smad-7 and regulating TGF-β/Smad signaling. Conclusion: These data provide new insights into the role of ADSCs-derived exosomes as an important player in VEGF-C-dependent lymphangiogenesis.

Lineage-specific exosomes promote the odontogenic differentiation of human dental pulp stem cells (DPSCs) through TGFβ1/smads signaling pathway via transfer of microRNAs

“…Exosomal miR-let7c attenuated kidney injury by significantly downregulated TGFβ1 and TGFR1 in the kidneys [38]. Exosomal miR-132 promoted lymphangiogenic response by directly targeting Smad-7 and regulating TGF-β/Smad signaling [39]. In the present study, there were 16 genes targeted by 15 differentially expressed microRNAs were involved in TGFβ signaling.…”

Autograft microskin combined with adipose-derived stem cell enhances wound healing in a full-thickness skin defect mouse model

“…4b, c). These cytokines have been confirmed that they play an essential role in promoting angiogenesis [35, 36]. Through GO enrichment analysis, we found that the biological process of DEPs in the MS+ADSC group was involved in cell migration, cellular component movement, and peptidyl-tyrosine phosphorylation.…”

The Role of Exosomes in the Crosstalk between Adipocytes and Liver Cancer Cells

“…Lymphangiogenesis could facilitate the stabilization of inflammatory cells and resolve tissue edema in acute and chronic inflammatory situations. Similarly, studies also showed that exosomes isolated from adipose-derived stem cells treated with vascular endothelial growth factor-C (VEGF-C) expressed more miRNA-132, which promotes lymphangiogenesis by regulating TGF-β/Smad signaling [66].…”