PXD042268

PXD042268 is an original dataset announced via ProteomeXchange.

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

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.

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]

submitter keyword: CTRP, LPS, macrophage, inflammation, transcriptomics, phosphoproteomics, signaling

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

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PRIDE project URI

• PRIDE
  1. PXD042268
     1. Label: PRIDE project
     2. Name: CTRP6 promotes macrophage inflammatory response and its deficiency attenuates LPS-induced inflammation