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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 02, 2023 |
| Title |
GM-CSF-activated STAT5A but not STAT5B regulates macrophage functions and inflammation in atherosclerosis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Inhibition of STAT5 was recently reported to reduce mouse atherosclerosis. However, the regulatory role of STAT5 isoforms STAT5A and STAT5B in human disease and more specifically in macrophages remains unknown. Here, we demonstrate reciprocal expression regulation of STAT5A and B in human atherosclerotic lesions. The former was highly upregulated in ruptured over stable plaque and correlated with macrophage presence, a finding that was corroborated by the high chromosomal accessibility of STAT5A but not B gene in plaque macrophages. Phosphorylated STAT5 correlated with macrophages confirming its activation status. As macrophage STAT5 is activated by GM-CSF, we studied the effects of its silencing in GM-CSF differentiated human macrophages. STAT5A knockdown blunted NF-kB pathway, phagocytosis, cholesterol metabolism, and apoptosis terms. These changes at transcriptional level could be confirmed at functional level, with significant increases in apoptosis and phagocytosis and decreases in lipid uptake and IL-6, IL8, and TNFa cytokine secretion after STAT5A knockdown. Finally, inhibition of general and isoform A specific STAT5 inhibitor significantly reduced the secretion of TNFa, IL-8 and IL-10 in ex vivo tissue slices of advanced human atherosclerotic plaques. In summary, we identify STAT5A as important determinant of macrophage functions and inflammation in the context of atherosclerosis and show its promise as therapeutic target for human atherosclerotic plaque inflammation.
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| Overall design |
Gene expression profiling using RNA-Seq. Human monocytes differentiated into macrophages with GM-CSF for 7 days and subsequent treatment with siRNA for 24h and an additional 24h resting period.
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| Contributor(s) |
Nagenborg J, Ruder A, Jin H, Mees B, Temmerman L, Donner M, Goossens P, Biessen E |
| Citation(s) |
37920458 |
| Submission date |
Nov 14, 2022 |
| Last update date |
Nov 16, 2023 |
| Contact name |
Han Jin |
| E-mail(s) |
han.jin@scilifelab.se
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| Organization name |
Science for Life Laboratory
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| Street address |
Tomtebodavägen 23
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| City |
Solna |
| ZIP/Postal code |
17165 |
| Country |
Sweden |
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| Platforms (1) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA901347 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE217893_exp_counts.tsv.gz |
266.2 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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