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Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 activation in endothelial cells: Amplification of low shear stress signaling by primary cilia
Endothelial cells are sensitive to mechanical stress and respond differently to oscillatory flow versus unidirectional flow. This review highlights the mechanisms by which a wide range of unidirectional laminar shear stress induces activation of the redox sensitive antioxidant transcription factor n...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379703/ https://www.ncbi.nlm.nih.gov/pubmed/34425388 http://dx.doi.org/10.1016/j.redox.2021.102103 |
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author | Ishii, Tetsuro Warabi, Eiji Mann, Giovanni E. |
author_facet | Ishii, Tetsuro Warabi, Eiji Mann, Giovanni E. |
author_sort | Ishii, Tetsuro |
collection | PubMed |
description | Endothelial cells are sensitive to mechanical stress and respond differently to oscillatory flow versus unidirectional flow. This review highlights the mechanisms by which a wide range of unidirectional laminar shear stress induces activation of the redox sensitive antioxidant transcription factor nuclear factor-E2-related factor 2 (Nrf2) in cultured endothelial cells. We propose that fibroblast growth factor-2 (FGF-2), brain-derived neurotrophic factor (BDNF) and 15-Deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) are potential Nrf2 activators induced by laminar shear stress. Shear stress-dependent secretion of FGF-2 and its receptor-mediated signaling is tightly controlled, requiring neutrophil elastase released by shear stress, αvβ3 integrin and the cell surface glycocalyx. We speculate that primary cilia respond to low laminar shear stress (<10 dyn/cm(2)), resulting in secretion of insulin-like growth factor 1 (IGF-1), which facilitates αvβ3 integrin-dependent FGF-2 secretion. Shear stress induces generation of heparan-binding epidermal growth factor-like growth factor (HB-EGF), which contributes to FGF-2 secretion and gene expression. Furthermore, HB-EGF signaling modulates FGF-2-mediated NADPH oxidase 1 activation that favors casein kinase 2 (CK2)-mediated phosphorylation/activation of Nrf2 associated with caveolin 1 in caveolae. Higher shear stress (>15 dyn/cm(2)) induces vesicular exocytosis of BDNF from endothelial cells, and we propose that BDNF via the p75(NTR) receptor could induce CK2-mediated Nrf2 activation. Unidirectional laminar shear stress upregulates gene expression of FGF-2 and BDNF and generation of 15d-PGJ(2), which cooperate in sustaining Nrf2 activation to protect endothelial cells against oxidative damage. |
format | Online Article Text |
id | pubmed-8379703 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-83797032021-08-27 Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 activation in endothelial cells: Amplification of low shear stress signaling by primary cilia Ishii, Tetsuro Warabi, Eiji Mann, Giovanni E. Redox Biol Review Article Endothelial cells are sensitive to mechanical stress and respond differently to oscillatory flow versus unidirectional flow. This review highlights the mechanisms by which a wide range of unidirectional laminar shear stress induces activation of the redox sensitive antioxidant transcription factor nuclear factor-E2-related factor 2 (Nrf2) in cultured endothelial cells. We propose that fibroblast growth factor-2 (FGF-2), brain-derived neurotrophic factor (BDNF) and 15-Deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) are potential Nrf2 activators induced by laminar shear stress. Shear stress-dependent secretion of FGF-2 and its receptor-mediated signaling is tightly controlled, requiring neutrophil elastase released by shear stress, αvβ3 integrin and the cell surface glycocalyx. We speculate that primary cilia respond to low laminar shear stress (<10 dyn/cm(2)), resulting in secretion of insulin-like growth factor 1 (IGF-1), which facilitates αvβ3 integrin-dependent FGF-2 secretion. Shear stress induces generation of heparan-binding epidermal growth factor-like growth factor (HB-EGF), which contributes to FGF-2 secretion and gene expression. Furthermore, HB-EGF signaling modulates FGF-2-mediated NADPH oxidase 1 activation that favors casein kinase 2 (CK2)-mediated phosphorylation/activation of Nrf2 associated with caveolin 1 in caveolae. Higher shear stress (>15 dyn/cm(2)) induces vesicular exocytosis of BDNF from endothelial cells, and we propose that BDNF via the p75(NTR) receptor could induce CK2-mediated Nrf2 activation. Unidirectional laminar shear stress upregulates gene expression of FGF-2 and BDNF and generation of 15d-PGJ(2), which cooperate in sustaining Nrf2 activation to protect endothelial cells against oxidative damage. Elsevier 2021-08-13 /pmc/articles/PMC8379703/ /pubmed/34425388 http://dx.doi.org/10.1016/j.redox.2021.102103 Text en © 2021 The Authors. Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Review Article Ishii, Tetsuro Warabi, Eiji Mann, Giovanni E. Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 activation in endothelial cells: Amplification of low shear stress signaling by primary cilia |
title | Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 activation in endothelial cells: Amplification of low shear stress signaling by primary cilia |
title_full | Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 activation in endothelial cells: Amplification of low shear stress signaling by primary cilia |
title_fullStr | Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 activation in endothelial cells: Amplification of low shear stress signaling by primary cilia |
title_full_unstemmed | Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 activation in endothelial cells: Amplification of low shear stress signaling by primary cilia |
title_short | Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 activation in endothelial cells: Amplification of low shear stress signaling by primary cilia |
title_sort | mechanisms underlying unidirectional laminar shear stress-mediated nrf2 activation in endothelial cells: amplification of low shear stress signaling by primary cilia |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379703/ https://www.ncbi.nlm.nih.gov/pubmed/34425388 http://dx.doi.org/10.1016/j.redox.2021.102103 |
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