Oscillatory shear stress induces the transition of EPCs into mesenchymal cells through ROS/PKCζ/p53 pathway
Copyright © 2020 Elsevier Inc. All rights reserved..
AIMS: Studies indicate that the pattern of shear stress determines the direction of endothelial progenitor cells (EPCs) differentiation. However, the mechanism remains largely unknown. Herein, we try to identify the role of oscillatory shear stress (OSS) in the transdifferentiation of EPCs into mesenchymal cells and the mechanism involved.
MATERIALS AND METHODS: OSS was applied to EPCs using the flow chamber system in vitro. Matrigel, Boyden chamber, and healing assay were used to observe the changes in EPCs function. Further, 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe and/or western blot were performed to detect the expression of reactive oxygen species (ROS), p53 and PKCζ in EPCs. EPCs transduced with Lentivirus carrying Tp53 were implanted into the arterial vessel in the balloon injured rat model, and neointimal thickening was verified by HE staining.
KEY FINDINGS: OSS enhanced the expression of mesenchymal cell markers alpha-smooth muscle actin (α-SMA) and smooth muscle 22 alpha (SM22α) on EPCs. In the meantime, OSS time-dependently decreased p53 expression in EPCs, which was partially abolished by treatment with ROS scavenger N-acetylcysteine (NAC) or protein kinase C zeta (PKCζ) inhibitor Go6983. Moreover, the p53 agonist tenovin-1 attenuated the changes of OSS-mediated the mesenchymal cell markers and EPCs function. Besides, we also found that transplanting EPCs transfected with LV-Tp53 significantly inhibited neointimal thickening and promoted reendothelialization in vivo.
SIGNIFICANCE: This study demonstrates OSS-induced EPC transdifferentiation into mesenchymal cells and ROS/PKCζ/p53 pathway play an essential role in it. It may serve as a promising therapeutic target for cardiovascular disease in the future.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:253 |
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| Enthalten in: |
Life sciences - 253(2020) vom: 15. Juli, Seite 117728 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gao, Yu [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.06.2020 Date Revised 10.06.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.lfs.2020.117728 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM309371511 |
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| 100 | 1 | |a Gao, Yu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Oscillatory shear stress induces the transition of EPCs into mesenchymal cells through ROS/PKCζ/p53 pathway |
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| 500 | |a Date Revised 10.06.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a AIMS: Studies indicate that the pattern of shear stress determines the direction of endothelial progenitor cells (EPCs) differentiation. However, the mechanism remains largely unknown. Herein, we try to identify the role of oscillatory shear stress (OSS) in the transdifferentiation of EPCs into mesenchymal cells and the mechanism involved | ||
| 520 | |a MATERIALS AND METHODS: OSS was applied to EPCs using the flow chamber system in vitro. Matrigel, Boyden chamber, and healing assay were used to observe the changes in EPCs function. Further, 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe and/or western blot were performed to detect the expression of reactive oxygen species (ROS), p53 and PKCζ in EPCs. EPCs transduced with Lentivirus carrying Tp53 were implanted into the arterial vessel in the balloon injured rat model, and neointimal thickening was verified by HE staining | ||
| 520 | |a KEY FINDINGS: OSS enhanced the expression of mesenchymal cell markers alpha-smooth muscle actin (α-SMA) and smooth muscle 22 alpha (SM22α) on EPCs. In the meantime, OSS time-dependently decreased p53 expression in EPCs, which was partially abolished by treatment with ROS scavenger N-acetylcysteine (NAC) or protein kinase C zeta (PKCζ) inhibitor Go6983. Moreover, the p53 agonist tenovin-1 attenuated the changes of OSS-mediated the mesenchymal cell markers and EPCs function. Besides, we also found that transplanting EPCs transfected with LV-Tp53 significantly inhibited neointimal thickening and promoted reendothelialization in vivo | ||
| 520 | |a SIGNIFICANCE: This study demonstrates OSS-induced EPC transdifferentiation into mesenchymal cells and ROS/PKCζ/p53 pathway play an essential role in it. It may serve as a promising therapeutic target for cardiovascular disease in the future | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Endothelial progenitor cells | |
| 650 | 4 | |a Endothelial-to-mesenchymal transition | |
| 650 | 4 | |a Oscillatory shear stress | |
| 650 | 4 | |a p53 | |
| 650 | 7 | |a Acetanilides |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
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| 700 | 1 | |a Cui, Xiaodong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Meiyue |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yaowen |e verfasserin |4 aut | |
| 700 | 1 | |a He, Yanting |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Lanlan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiaoyun |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Min |e verfasserin |4 aut | |
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