{"title":"WISP1 promotes the progression of rheumatoid arthritis through NLRP3 inflammasome activation","authors":"Tiantian Hao , Jianhua Niu , Zizheng Tang , Kangqi Xie , Hongxia Chen , Hui Wang","doi":"10.1016/j.molimm.2025.02.004","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease without effective treatments. This study explored WNT1 inducible signaling pathway protein 1 (WISP1) as a potential target to prevent RA.</div></div><div><h3>Methods</h3><div>AAV-shRNA-WISP1 or AAV-NC was injected in each ankle of collagen-induced arthritis (CIA) rats. Si-WISP1 or NC vector was transfected to TNF-α-induced fibroblast-like synoviocytes (FLSs). The effects of WISP1 knockdown on levels of pro-inflammatory factors in rats or FLSs were examined by qRT-PCR, ELISA, and western blot. CCK-8, Wound-healing, and transwell assays were used to estimate the effects of WISP1 knockdown on TNF-α-induced cell vitality, migration, and invasion in FLSs. The NLRP3 inflammasome-related proteins were checked by immunohistochemistry, immunofluorescence assay, and western blot in rats or FLSs.</div></div><div><h3>Findings</h3><div>Administration of WISP1 knockdown improved joint damage and diminished synovial inflammation in CIA rats. WISP1 knockdown restrained TNF-α-induced cell vitality, migration, and invasion in FLSs. In CIA rats and TNFα-induced FLSs, WISP1 knockdown reduced the secretion of inflammatory factors and restrained NLRP3 inflammasome activation.</div></div><div><h3>Interpretation</h3><div>WISP1 knockdown effectively inhibited NLRP3 inflammasome activation and inflammatory factors levels.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"179 ","pages":"Pages 106-115"},"PeriodicalIF":3.2000,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0161589025000288","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Rheumatoid arthritis (RA) is a chronic autoimmune disease without effective treatments. This study explored WNT1 inducible signaling pathway protein 1 (WISP1) as a potential target to prevent RA.
Methods
AAV-shRNA-WISP1 or AAV-NC was injected in each ankle of collagen-induced arthritis (CIA) rats. Si-WISP1 or NC vector was transfected to TNF-α-induced fibroblast-like synoviocytes (FLSs). The effects of WISP1 knockdown on levels of pro-inflammatory factors in rats or FLSs were examined by qRT-PCR, ELISA, and western blot. CCK-8, Wound-healing, and transwell assays were used to estimate the effects of WISP1 knockdown on TNF-α-induced cell vitality, migration, and invasion in FLSs. The NLRP3 inflammasome-related proteins were checked by immunohistochemistry, immunofluorescence assay, and western blot in rats or FLSs.
Findings
Administration of WISP1 knockdown improved joint damage and diminished synovial inflammation in CIA rats. WISP1 knockdown restrained TNF-α-induced cell vitality, migration, and invasion in FLSs. In CIA rats and TNFα-induced FLSs, WISP1 knockdown reduced the secretion of inflammatory factors and restrained NLRP3 inflammasome activation.
期刊介绍:
Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to:
Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology
Mechanisms of induction, regulation and termination of innate and adaptive immunity
Intercellular communication, cooperation and regulation
Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc)
Mechanisms of action of the cells and molecules of the immune system
Structural analysis
Development of the immune system
Comparative immunology and evolution of the immune system
"Omics" studies and bioinformatics
Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc)
Technical developments.