Quantitative Proteomic Analysis of Synovial Tissue Reveals That Upregulated OLFM4 Aggravates Inflammation in Rheumatoid Arthritis.
Xiaoyu RenManman GengKe XuChao LuYuanyuan ChengLinbo KongYongsong CaiWeikun HouYufeng LuYirixiati AihaitiPeng XuPublished in: Journal of proteome research (2021)
Tandem mass tag (TMT)-coupled liquid chromatography coupled with tandem mass spectrometry is a powerful method to investigate synovial tissue protein profiles in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Protein was isolated from synovial tissue samples of 22 patients and labeled with a TMT kit. Over 500 proteins were identified as the differential expression protein on comparing RA and OA synovial tissue, including 239 upregulated and 271 downregulated proteins. Data are available via ProteomeXchange with identifier PXD027703. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis showed that the majority participated in the developmental processes and protein processing in the endoplasmic reticulum. Olfactomedin 4 (OLFM4), a secreted glycoprotein, in joint inflammation of RA was explored. OLFM4 was upregulated in RA synovial tissue samples. In fibroblast-like synoviocytes (FLS), inflammation cytokines, TNF-α, interleukin (IL)-1β, and LPS can upregulate OLFM4. After OLFM4 knockdown under TNF-α stimulation, RA FLS proliferation was inhibited and the expression of CXCL9, CXCL11, and MMP-1 was decreased. Overall, the RA synovial tissue protein expression profile by proteomic analysis shows some unique targets in RA pathophysiology, and OLFM4 in FLS plays an important role in RA joint inflammation. OLFM4 can be a promising therapeutic target in RA synovial tissue.
Keyphrases
- rheumatoid arthritis
- disease activity
- ankylosing spondylitis
- oxidative stress
- interstitial lung disease
- tandem mass spectrometry
- liquid chromatography
- protein protein
- binding protein
- genome wide
- systemic lupus erythematosus
- amino acid
- gene expression
- end stage renal disease
- signaling pathway
- ultra high performance liquid chromatography
- dna methylation
- peritoneal dialysis
- small molecule
- poor prognosis
- inflammatory response
- transcription factor
- electronic health record
- high performance liquid chromatography
- ms ms
- patient reported
- knee osteoarthritis
- simultaneous determination
- prognostic factors
- newly diagnosed
- deep learning
- genome wide identification
- gas chromatography