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| Status |
Public on Oct 02, 2023 |
| Title |
CYR61 orchestrates NASH fibrosis through SYK-NFκB-PDGF signaling in monocyte-derived macrophages [HIVE single-cell RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Obesity is increasing worldwide and leads to a multitude of metabolic diseases including non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatosis (NASH). Here we examine the role of CYR61 in liver fibrosis and inflammation and its potential as a therapeutic target. Loss of CYR61 during NASH injury improves glucose tolerance, decreases liver inflammation and reduces fibrosis. CYR61 activates signaling in monocytes and monocyte-derived macrophages promoting a pro-inflammatory/pro-fibrotic phenotype through a CYR61/SYK/NFKB signaling cascade. In vitro, CYR61 activates Pdgfa and Pdgfb expression in macrophages in a NFκB-dependent manner. Ultimately, we identify a potential therapeutic for NASH: a CYR61-blocking antibody that reduces fibrotic injury and CYR61-driven signaling in macrophages in vitro and in vivo. This study demonstrates that CYR61 is a key driver of liver inflammation and fibrosis and a strong therapeutic target for treatment of NAFLD/NASH.
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| Overall design |
HIVE single-cell RNA-seq with two conditions: Control and CYR61, with four repeats each.
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| Contributor(s) |
Mooring M, Luukkonen P, Liu S, Balogun O, Mo R, Nejak-Bowen K, Poyurovsky M, Booth C, Konnikova L, Shulman GI, Yimlamai D |
| Citation(s) |
37756381 |
| |
| Submission date |
Mar 28, 2022 |
| Last update date |
Oct 03, 2023 |
| Contact name |
Shuchang Liu |
| E-mail(s) |
shl96@pitt.edu
|
| Organization name |
University of Pittsburgh
|
| Street address |
203 Lothrop Street
|
| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15261 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE199640 |
CYR61 orchestrates NASH fibrosis through SYK-NFκB-PDGF signaling in monocyte-derived macrophages |
|
| Relations |
| BioProject |
PRJNA820906 |
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