Exosomes from Adipose-Derived Stem Cells Promotes VEGF-C-Dependent Lymphangiogenesis by Regulating miRNA-132/TGF-β Pathway
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 be...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2018-08-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/492851 |
| _version_ | 1819001013026160640 |
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| author | Xiaolei Wang Haichao Wang Jingli Cao Chen Ye |
| author_facet | Xiaolei Wang Haichao Wang Jingli Cao Chen Ye |
| author_sort | Xiaolei Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T22:42:27Z |
| format | Article |
| id | doaj.art-1d4f0c5e6faa4ce6bbdc9626a7e44eb6 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-20T22:42:27Z |
| publishDate | 2018-08-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-1d4f0c5e6faa4ce6bbdc9626a7e44eb62022-12-21T19:24:26ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-08-0149116017110.1159/000492851492851Exosomes from Adipose-Derived Stem Cells Promotes VEGF-C-Dependent Lymphangiogenesis by Regulating miRNA-132/TGF-β PathwayXiaolei WangHaichao WangJingli CaoChen YeBackground/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.https://www.karger.com/Article/FullText/492851Adipose-derived stem cellsLymphangiogenesisVEGF-CmiR-132Exosome |
| spellingShingle | Xiaolei Wang Haichao Wang Jingli Cao Chen Ye Exosomes from Adipose-Derived Stem Cells Promotes VEGF-C-Dependent Lymphangiogenesis by Regulating miRNA-132/TGF-β Pathway Cellular Physiology and Biochemistry Adipose-derived stem cells Lymphangiogenesis VEGF-C miR-132 Exosome |
| title | Exosomes from Adipose-Derived Stem Cells Promotes VEGF-C-Dependent Lymphangiogenesis by Regulating miRNA-132/TGF-β Pathway |
| title_full | Exosomes from Adipose-Derived Stem Cells Promotes VEGF-C-Dependent Lymphangiogenesis by Regulating miRNA-132/TGF-β Pathway |
| title_fullStr | Exosomes from Adipose-Derived Stem Cells Promotes VEGF-C-Dependent Lymphangiogenesis by Regulating miRNA-132/TGF-β Pathway |
| title_full_unstemmed | Exosomes from Adipose-Derived Stem Cells Promotes VEGF-C-Dependent Lymphangiogenesis by Regulating miRNA-132/TGF-β Pathway |
| title_short | Exosomes from Adipose-Derived Stem Cells Promotes VEGF-C-Dependent Lymphangiogenesis by Regulating miRNA-132/TGF-β Pathway |
| title_sort | exosomes from adipose derived stem cells promotes vegf c dependent lymphangiogenesis by regulating mirna 132 tgf β pathway |
| topic | Adipose-derived stem cells Lymphangiogenesis VEGF-C miR-132 Exosome |
| url | https://www.karger.com/Article/FullText/492851 |
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