Integrin β3 Mediates the Endothelial-to-Mesenchymal Transition via the Notch Pathway

Autor: Weisen Wang, Zhi Wang, Dingyuan Tian, Xi Zeng, Yangdong Liu, Qining Fu, Anlin Liang, Yi Zhang, Qiangguo Gao, Jizhong Cheng, Yun Wang
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Cellular Physiology and Biochemistry, Vol 49, Iss 3, Pp 985-997 (2018)
Druh dokumentu: article
ISSN: 1015-8987
1421-9778
DOI: 10.1159/000493229
Popis: 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.
Databáze: Directory of Open Access Journals
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