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

Cellular Physiology and Biochemistry

Xiaolei  Wang¹ 

关键词: Adipose-derived stem cells;    Lymphangiogenesis;    VEGF-C;    miR-132;    Exosome;   

DOI  :  10.1159/000492851

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND