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Status |
Public on Nov 30, 2021 |
Title |
Next Generation Sequencing Fascilitates Quantitative Analysis of Differential Gene Expression in Human Pericytes treated with PDGF-BB |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
PDGF-BB: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 used tissue microarrays from control and AD brains to determine if PDGF-BB:PDGFRβ signalling components were altered in AD, and found that there was a reduction in vascular expression of PDGFB. We hypothesised that reduced PDGF-BB:PDGFRβ signalling in pericytes may have an impact on functions related to the BBB. We therefore tested the effects of PDGF-BB on primary human brain pericytes in vitro to define important signalling pathways and outcomes related to BBB function. Pericytes demonstrate a biphasic response to PDGF-BB, predominantly dependent on Akt and ERK. We determined that the actions of PDGF-BB are on-target at PDGFRβ, leading to internalisation and degradation of PDGFRβ. Using pharmacological inhibitors, we dissected distinct aspects of the PDGF-BB response that are controlled by ERK and Akt pathways. PDGF-BB promotes the proliferation of pericytes and protection from toxic stimuli through ERK signalling. In contrast, PDGF-BB:PDGFRβ signalling through Akt and NF-κB augments pericyte-derived inflammatory secretions. It may therefore be possible to supplement PDGF-BB or small molecule agonists to stabilise the cerebrovasculature in AD.
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Overall design |
mRNA profiles of post-mortem human pericytes treated with PDGF-BB at 1hr and 24hr
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Contributor(s) |
Smyth LC, Wu J, Curtis M, Faull RL, Dragunow M |
Citation missing |
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Submission date |
Nov 28, 2021 |
Last update date |
Nov 30, 2021 |
Contact name |
Leon Smyth |
E-mail(s) |
leon.smyth@otago.ac.nz
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Organization name |
University of Auckland
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Street address |
85 Park Road
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City |
Auckland |
ZIP/Postal code |
1023 |
Country |
New Zealand |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (9)
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Relations |
BioProject |
PRJNA784268 |