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Series GSE189712 Query DataSets for GSE189712
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
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.
 
Overall design mRNA profiles of post-mortem human pericytes treated with PDGF-BB at 1hr and 24hr
 
Contributor(s) Smyth LC, Wu J, Curtis M, Faull RL, Dragunow M
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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
Organization name University of Auckland
Street address 85 Park Road
City Auckland
ZIP/Postal code 1023
Country New Zealand
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (9)
GSM5706281 H189 Veh (CS365)
GSM5706282 H189 PDGF-BB 10 ng/mL 1 h (CS366)
GSM5706283 H189 PDGF-BB 10 ng/mL 24 h (CS367)
Relations
BioProject PRJNA784268

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Supplementary file Size Download File type/resource
GSE189712_full_table_PDGFRBB.txt.gz 1.8 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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