Integrin β3 Mediates the Endothelial-to-Mesenchymal Transition via the Notch Pathway
© 2018 The Author(s). Published by S. Karger AG, Basel..
BACKGROUND/AIMS: Neointimal hyperplasia is responsible for stenosis, which requires corrective vascular surgery, and is also a major morphological feature of many cardiovascular diseases. This hyperplasia involves the endothelial-to-mesenchymal transition (EndMT). We investigated whether integrin β3 can modulate the EndMT, as well as its underlying mechanism.
METHODS: Integrin β3 was overexpressed or knocked down in human umbilical vein endothelial cells (HUVECs). The expression of endothelial markers and mesenchymal markers was determined by real-time reverse transcription PCR (RT-PCR), immunofluorescence staining, and western blot analysis. Notch signaling pathway components were detected by real-time RT-PCR and western blot analysis. Cell mobility was evaluated by wound-healing, Transwell, and spreading assays. Fibroblast-specific protein 1 (FSP-1) promoter activity was determined by luciferase assay.
RESULTS: Transforming growth factor (TGF)-β1 treatment or integrin β3 overexpression significantly promoted the EndMT by downregulating VE-cadherin and CD31 and upregulating smooth muscle actin α and FSP-1 in HUVECs, and by enhancing cell migration. Knockdown of integrin β3 reversed these effects. Notch signaling was activated after TGF-β1 treatment of HUVECs. Knockdown of integrin β3 suppressed TGF-β1-induced Notch activation and expression of the Notch downstream target FSP-1.
CONCLUSION: Integrin β3 may promote the EndMT in HUVECs through activation of the Notch signaling pathway.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:49 |
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| Enthalten in: |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology - 49(2018), 3 vom: 02., Seite 985 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Weisen [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.10.2018 Date Revised 30.01.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1159/000493229 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM288336445 |
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| 245 | 1 | 0 | |a Integrin β3 Mediates the Endothelial-to-Mesenchymal Transition via the Notch Pathway |
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| 500 | |a Date Completed 12.10.2018 | ||
| 500 | |a Date Revised 30.01.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2018 The Author(s). Published by S. Karger AG, Basel. | ||
| 520 | |a BACKGROUND/AIMS: Neointimal hyperplasia is responsible for stenosis, which requires corrective vascular surgery, and is also a major morphological feature of many cardiovascular diseases. This hyperplasia involves the endothelial-to-mesenchymal transition (EndMT). We investigated whether integrin β3 can modulate the EndMT, as well as its underlying mechanism | ||
| 520 | |a METHODS: Integrin β3 was overexpressed or knocked down in human umbilical vein endothelial cells (HUVECs). The expression of endothelial markers and mesenchymal markers was determined by real-time reverse transcription PCR (RT-PCR), immunofluorescence staining, and western blot analysis. Notch signaling pathway components were detected by real-time RT-PCR and western blot analysis. Cell mobility was evaluated by wound-healing, Transwell, and spreading assays. Fibroblast-specific protein 1 (FSP-1) promoter activity was determined by luciferase assay | ||
| 520 | |a RESULTS: Transforming growth factor (TGF)-β1 treatment or integrin β3 overexpression significantly promoted the EndMT by downregulating VE-cadherin and CD31 and upregulating smooth muscle actin α and FSP-1 in HUVECs, and by enhancing cell migration. Knockdown of integrin β3 reversed these effects. Notch signaling was activated after TGF-β1 treatment of HUVECs. Knockdown of integrin β3 suppressed TGF-β1-induced Notch activation and expression of the Notch downstream target FSP-1 | ||
| 520 | |a CONCLUSION: Integrin β3 may promote the EndMT in HUVECs through activation of the Notch signaling pathway | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Integrin β3 | |
| 650 | 4 | |a Notch signaling pathway | |
| 650 | 4 | |a endothelial cells | |
| 650 | 4 | |a endothelial-to-mesenchymal transition | |
| 650 | 4 | |a neointimal hyperplasia | |
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| 700 | 1 | |a Wang, Zhi |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Dingyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Xi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yangdong |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Qining |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Anlin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Qiangguo |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Jizhong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yun |e verfasserin |4 aut | |
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