PXD042268 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | CTRP6 promotes macrophage inflammatory response and its deficiency attenuates LPS-induced inflammation |
Description | Macrophages play critical roles in inflammation and tissue homeostasis, and their functions are regulated by various autocrine, paracrine, and endocrine factors. We have previously shown that CTRP6, a secreted protein of the C1q family, targets both adipocytes and macrophages to promote obesity-linked inflammation in adipose tissue. However, the gene programs and signaling pathways directly regulated by CTRP6 in macrophage remain unknown. Here, we combine transcriptomic and phosphoproteomic analyses to show that CTRP6 activates inflammatory gene programs and signaling pathways in bone marrow-derived macrophages (BMDMs). Treatment of BMDMs with CTRP6 upregulates proinflammatory, and suppresses the anti-inflammatory, gene expression. We show that CTRP6 activates p44/42-MAPK, p38-MAPK, and NF-κB signalings to promote inflammatory cytokine secretion from BMDMs, and that pharmacologic inhibition of these signaling pathways largely abolish the effects of CTRP6. Pretreatment of BMDMs with CTRP6 further augments LPS-induced inflammatory signaling and cytokine secretion from BMDMs. Consistent with the metabolic phenotype of proinflammatory M1-like macrophages, CTRP6 treatment induces a shift toward aerobic glycolysis and lactate production, reduces oxidative metabolism, and elevates mitochondrial ROS production in BMDMs. We use a Ctrp6 knockout mouse model to further confirm the physiologic relevance of our in vitro findings. BMDMs from CTRP6-deficient mice are less inflammatory at baseline and show a marked suppression of LPS-induced inflammatory gene expression and cytokine secretion. Loss of CTRP6 in mice also dampens LPS-induced inflammation and hypothermia. Collectively, we provide mechanistic evidence that CTRP6 regulates macrophage function, and neutralizing CTRP6 activity may have beneficial effects in reducing inflammation. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:27:21.117.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jun Zhong |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | phosphorylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-05-16 11:28:33 | ID requested | |
1 | 2024-01-26 10:21:27 | announced | |
⏵ 2 | 2024-10-22 06:27:24 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.1016/j.jbc.2023.105566; |
Xu C, Sarver DC, Lei X, Sahagun A, Zhong J, Na CH, Rudich A, Wong GW, CTRP6 promotes the macrophage inflammatory response, and its deficiency attenuates LPS-induced inflammation. J Biol Chem, 300(1):105566(2024) [pubmed] |
Keyword List
submitter keyword: CTRP, LPS, macrophage, inflammation, transcriptomics, phosphoproteomics, signaling |
Contact List
G. William Wong |
contact affiliation | 1Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA |
contact email | gwwong@jhmi.edu |
lab head | |
Jun Zhong |
contact affiliation | Delta Omics Inc |
contact email | jzhong@deltaomics.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD042268
- Label: PRIDE project
- Name: CTRP6 promotes macrophage inflammatory response and its deficiency attenuates LPS-induced inflammation