Characterisation of PDGF-BB:PDGFRβ signalling pathways in human brain pericytes : evidence of disruption in Alzheimer's disease
© 2022. The Author(s)..
Platelet-derived growth factor-BB (PDGF-BB):PDGF receptor-β (PDGFRβ) signalling in brain pericytes is critical to the development, maintenance and function of a healthy blood-brain barrier (BBB). Furthermore, BBB impairment and pericyte loss in Alzheimer's disease (AD) is well documented. We found that PDGF-BB:PDGFRβ signalling components were altered in human AD brains, with a marked reduction in vascular PDGFB. We hypothesised that reduced PDGF-BB:PDGFRβ signalling in pericytes may impact on the BBB. We therefore tested the effects of PDGF-BB on primary human brain pericytes in vitro to define pathways related to BBB function. Using pharmacological inhibitors, we dissected distinct aspects of the PDGF-BB response that are controlled by extracellular signal-regulated kinase (ERK) and Akt pathways. PDGF-BB promotes the proliferation of pericytes and protection from apoptosis through ERK signalling. In contrast, PDGF-BB:PDGFRβ signalling through Akt augments pericyte-derived inflammatory secretions. It may therefore be possible to supplement PDGF-BB signalling to stabilise the cerebrovasculature in AD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
Communications biology - 5(2022), 1 vom: 17. März, Seite 235 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Smyth, Leon C D [VerfasserIn] |
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| Links: |
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| Themen: |
1B56C968OA |
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| Anmerkungen: |
Date Completed 05.04.2022 Date Revised 12.11.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s42003-022-03180-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM338320601 |
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| 100 | 1 | |a Smyth, Leon C D |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Characterisation of PDGF-BB:PDGFRβ signalling pathways in human brain pericytes |b evidence of disruption in Alzheimer's disease |
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| 500 | |a Date Revised 12.11.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a Platelet-derived growth factor-BB (PDGF-BB):PDGF receptor-β (PDGFRβ) signalling in brain pericytes is critical to the development, maintenance and function of a healthy blood-brain barrier (BBB). Furthermore, BBB impairment and pericyte loss in Alzheimer's disease (AD) is well documented. We found that PDGF-BB:PDGFRβ signalling components were altered in human AD brains, with a marked reduction in vascular PDGFB. We hypothesised that reduced PDGF-BB:PDGFRβ signalling in pericytes may impact on the BBB. We therefore tested the effects of PDGF-BB on primary human brain pericytes in vitro to define pathways related to BBB function. Using pharmacological inhibitors, we dissected distinct aspects of the PDGF-BB response that are controlled by extracellular signal-regulated kinase (ERK) and Akt pathways. PDGF-BB promotes the proliferation of pericytes and protection from apoptosis through ERK signalling. In contrast, PDGF-BB:PDGFRβ signalling through Akt augments pericyte-derived inflammatory secretions. It may therefore be possible to supplement PDGF-BB signalling to stabilise the cerebrovasculature in AD | ||
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| 700 | 1 | |a Rustenhoven, Justin |e verfasserin |4 aut | |
| 700 | 1 | |a Aalderink, Miranda |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Adelie |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Rebecca |e verfasserin |4 aut | |
| 700 | 1 | |a Coppieters, Natacha |e verfasserin |4 aut | |
| 700 | 1 | |a Handley, Renee |e verfasserin |4 aut | |
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| 700 | 1 | |a Singh-Bains, Malvindar K |e verfasserin |4 aut | |
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| 700 | 1 | |a Turner, Clinton |e verfasserin |4 aut | |
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| 700 | 1 | |a Dragunow, Mike |e verfasserin |4 aut | |
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