Dataset Information

Capsaicin ameliorates rheumatoid arthritis via ROS-mediated apoptosis in fibroblast-like synoviocytes

ABSTRACT: In this project we discovered that CAP not only reduces joint swelling in arthritic model mice but also exhibits anti-inflammatory and antiproliferative effects on fibroblast-like synoviocytes (FLS). By synthesizing alkyne-tagged CAP probes and employing activity-based protein profiling (ABPP), we identified and confirmed that CAP binds to PRDX2, inhibiting its antioxidant function and thereby inducing cellular oxidative stress and apoptosis, which contribute to its anti-arthritic effects. Furthermore, we found that the PRDX2 inhibitor, Conoidin A (ConA), produces similar effects. The results indicate that PRDX2 serve as a potential target for capsaicin to therapeutic intervention in rheumatoid arthritis.

ORGANISM(S): Homo Sapiens

SUBMITTER: Jigang Wang

PROVIDER: PXD057639 | iProX | Thu Nov 07 00:00:00 GMT 2024

REPOSITORIES: iProX

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Publications

Inhibition Peroxiredoxin-2 by Capsaicin Ameliorates Rheumatoid Arthritis via ROS-Mediated Apoptosis in Fibroblast-Like Synoviocytes.

He Hengkai H Hao Mingjing M Luo Piao P Chen Junhui J An Yehai Y Huang Jingnan J He Ruiyi R Du Qingfeng Q Zhang Qian Q Wang Jigang J

MedComm 20250529 6

Rheumatoid arthritis (RA), a prevalent and incurable autoimmune disease globally, is characterized by the immune system attacking the body's own tissues, leading to joint inflammation and damage. Capsaicin (CAP), from <i>Capsicum annuum L</i>., is known for its burning sensation-inducing property and has shown various pharmacological effects, yet its specific mechanisms and targets in RA treatment remain largely unclear. This study aimed to investigate the role of CAP in RA by synthesizing CAP p ...[more]

PMID: 40443720

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Project description:Rheumatoid synoviocytes, which consist of fibroblast-like synoviocytes (FLS) and synovial macrophages (SM), are crucial for the progression of rheumatoid arthritis (RA). Particularly, FLS of RA patients (RA-FLS) exhibit invasive characteristics reminiscent of cancer cells, destroying cartilage and bone, although it remains unresolved how RA-FLS exhibit invasive phenotype. RA-FLS and SM originate differently from mesenchymal and myeloid cells, respectively, but share many pathologic functions. However, the molecular signatures and biological networks representing the distinct and shared features of the two cell types are unknown. Presently, we performed global transcriptome profiling of FLS and SM obtained from RA and osteoarthritis patients. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining invasiveness of RA-FLS and pro-inflammatory properties of RA synovial macrophages (RA-SM), respectively. Interestingly, under interleukin1β-stimulated condition, RA-FLS newly acquired pro-inflammatory signature mimicking RA-SM without losing invasive properties. We next reconstructed a network model that delineates the shared, RA-FLS-dominant (invasive), and RA-SM-dominant (inflammatory) processes. From the network model, we selected 13 genes, including POSTN and TWIST1, as novel regulator candidates responsible for FLS invasiveness. Of note, POSTN and TWIST1 expressions were elevated in independent RA-FLS and were further instigated by interleukin1β. In vitro functional assays demonstrated the requirement of POSTN and TWIST1 for migration and invasion of RA-FLS stimulated with interleukin1β. Taken together, our systems approach to rheumatoid synovitis provides a basis for identifying novel regulators responsible for pathological features of RA-FLS and RA-SM, demonstrating how a certain type of cells acquires functional redundancy under chronic inflammatory conditions. To identify molecular signatures of FLS and MLS in RA joints, we isolated FLS from synovial tissues of RA and osteoarthritis (OA) patients, obtained synovial macrophages from synovial fluid of RA patients, and differentiated control macrophages from peripheral blood of healthy subjects. Also, we stimulated FLS with IL1β, and then analyzed gene expression profiles of both IL1β-stimulated RA-FLS and OA-FLS

Dataset Information

Capsaicin ameliorates rheumatoid arthritis via ROS-mediated apoptosis in fibroblast-like synoviocytes

Publications

Inhibition Peroxiredoxin-2 by Capsaicin Ameliorates Rheumatoid Arthritis via ROS-Mediated Apoptosis in Fibroblast-Like Synoviocytes.

Similar Datasets

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