PXD055569

PXD055569 is an original dataset announced via ProteomeXchange.

Title	Bone-protective effects of neutralizing angiopoietin-like protein 4 monoclonal antibody in rheumatoid arthritis
Description	Despite recent advances, rheumatoid arthritis (RA) patients remain refractory to therapy. Dysregulated overproduction of angiopoietin-like 4 protein (ANGPTL4) is thought to be contributed to the disease development. Therefore, interference with ANGPTL4 biological function may constitute a new therapeutic strategy for this disease. ANGPTL4 was initially identified as a regulator of lipid metabolism, which is hydrolyzed to N-terminal (nANGPTL4) and C-terminal (cANGPTL4) fragments in vivo. cANGPTL4 is involved in several non-lipid-related processes, including angiogenesis and inflammation. In this study, we analyzed the mRNA expression of ANGPTL4 in synovial tissue of RA in comparison to healthy individuals of the Gene Expression Omnibus (GEO) database. The results indicated that the mRNA expression of ANGPTL4 is increased in RA synovial tissues. The level of ANGPTL4 was found to be overexpressed in the sera and synovial tissues from patients with RA versus controls. A neutralizing antibody against cANGPTL4 (anti-cANGPTL4 Ab) was employed to treat arthritis animal models, including collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA), respectively. The results demonstrated that the anti-cANGPTL4 Ab inhibited inflammation and bone loss in two models. Transcriptomic and proteomic profiling of synovial tissues from AIA model indicated that the anti-cANGPTL4 Ab inhibited fibroblast-like synoviocyte (FLS) immigration and inflammatory-induced osteoclastogenesis. These data collectively identify ANGPTL4 as a potential biomarker for the diagnosis of RA, and targeting cANGPTL4 may represent a novel therapeutic strategy.
HostingRepository	iProX
AnnounceDate	2024-09-05
AnnouncementXML	Submission_2024-10-24_23:32:48.113.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wenxiang Cheng
SpeciesList	scientific name: Rattus norvegicus; NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-04 18:57:45	ID requested
⏵ 1	2024-10-24 23:45:56	announced

Ke L, He Q, Qu J, Wang X, Li K, Gong X, Li L, Xu J, Yu Q, Yu H, Lin X, Li J, Tan NS, Sun W, Li L, Zhang P, Cheng W, Bone-protective effects of neutralizing angiopoietin-like protein 4 monoclonal antibody in rheumatoid arthritis. Mol Ther, 32(12):4497-4513(2024) [pubmed]

submitter keyword: Rheumatoid Arthritis, ANGPTL4, Biologic therapy, Bone protection, Inflammation

Wenxiang Cheng
contact affiliation	Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
contact email	wx.cheng@siat.ac.cn
lab head
Wenxiang Cheng
contact affiliation	Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences
contact email	wx.cheng@siat.ac.cn
dataset submitter

iProX dataset URI