ArticleCellular & molecular immunology2022
Extracellular sulfatase-2 is overexpressed in rheumatoid arthritis and mediates the TNF-α-induced inflammatory activation of synovial fibroblasts.
Article in Cellular & molecular immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Identification of diagnostic and prognostic hub genes in osteoarthritis: an integrated bioinformatics study.Clinical rheumatology · 2026Article
- The "Tianyu" Formulation Alleviates Rheumatoid Arthritis by Modulating the NLRP3/Caspase-1/GSDMD-Mediated Pyroptosis Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- TWEAK receptor (Fn14) exacerbates TNF-α-induced inflammation in rheumatoid arthritis synovial fibroblasts and influences response to anti-TNF-α therapy.Cellular & molecular immunology · 2026Article
- Targeting the synovial engine: next-generation engineered immune cells to eradicate pathogenic FLS in rheumatoid arthritis, with safety-first, selective designs.Frontiers in immunology · 2026Review
- The single-cell landscape of the human vein after arteriovenous fistula creation and implications for maturation failure.Kidney international · 2026Article
- Vinburnine Sensitizes Radiotherapy Efficacy in Nasopharyngeal Carcinoma by Triggering Pyroptosis and Immune Responses via Activation of EDAR-NFκB Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Heparan-6-O-endosulfatase 2, a cancer-related proteoglycan enzyme, is effectively inhibited by a specific sea cucumber fucosylated glycosaminoglycan.Glycobiology · 2025Article
- Beneficial Probiotics with New Cancer Therapies for Improved Treatment of Hepatocellular Carcinoma.Diseases (Basel, Switzerland) · 2025Review
- Editor's Choice Development of a method to measure the activity of heparan sulfate 6-endosulfatase for biological research.Glycobiology · 2025Article
- The extracellular heparan sulfatase SULF2 limits myeloid IFNβ signaling and Th17 responses in inflammatory arthritis.Cellular and molecular life sciences : CMLS · 2024Article
- Manipulating host secreted protein gene expression: an indirect approach by HPV11/16 E6/E7 to suppress PBMC cytokine secretion.Virology journal · 2024Article
- PA28γ induces dendritic cell maturation and activates T-cell immune responses in oral lichen planus.MedComm · 2024Article
- Pharmacological evaluation and phytochemical profiling of butanol extract of L. edodes with in- silico virtual screening.Scientific reports · 2024Article
- The therapeutic effect of Loranthus parasiticus lignan derivatives on collagen-induced arthritis in rats through the SHBG/NFκB pathway.Inflammopharmacology · 2024Article
- The genetic architecture of complete blood counts in lactating Holstein dairy cows.Frontiers in genetics · 2024Article
- Article
- Ferroptosis-Related Molecular Clusters and Diagnostic Model in Rheumatoid Arthritis.International journal of molecular sciences · 2023Article
- Sulf2 mediates the effects of TNF in RASFs.Nature reviews. Rheumatology · 2022Article
- Inflammation-Driven Secretion Potential Is Upregulated in Osteoarthritic Fibroblast-Like Synoviocytes.International journal of molecular sciences · 2022Article
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13 authors at 6 institutions in 1 country.
Funding
Abstract
Extracellular sulfatase-2 (Sulf-2) influences receptor-ligand binding and subsequent signaling by chemokines and growth factors, yet Sulf-2 remains unexplored in inflammatory cytokine signaling in the context of rheumatoid arthritis (RA). In the present study, we characterized Sulf-2 expression in RA and investigated its potential role in TNF-α-induced synovial inflammation using primary human RA synovial fibroblasts (RASFs). Sulf-2 expression was significantly higher in serum and synovial tissues from patients with RA and in synovium and serum from hTNFtg mice. RNA sequencing analysis of TNF-α-stimulated RASFs showed that Sulf-2 siRNA modulated ~2500 genes compared to scrambled siRNA. Ingenuity Pathway Analysis of RNA sequencing data identified Sulf-2 as a primary target in fibroblasts and macrophages in RA. Western blot, ELISA, and qRT‒PCR analyses confirmed that Sulf-2 knockdown reduced the TNF-α-induced expression of ICAM1, VCAM1, CAD11, PDPN, CCL5, CX3CL1, CXCL10, and CXCL11. Signaling studies identified the protein kinase C-delta (PKCδ) and c-Jun N-terminal kinase (JNK) pathways as key in the TNF-α-mediated induction of proteins related to cellular adhesion and invasion. Knockdown of Sulf-2 abrogated TNF-α-induced RASF proliferation. Sulf-2 knockdown with siRNA and inhibition by OKN-007 suppressed the TNF-α-induced phosphorylation of PKCδ and JNK, thereby suppressing the nuclear translocation and DNA binding activity of the transcription factors AP-1 and NF-κBp65 in human RASFs. Interestingly, Sulf-2 expression positively correlated with the expression of TNF receptor 1, and coimmunoprecipitation assays demonstrated the binding of these two proteins, suggesting they exhibit crosstalk in TNF-α signaling. This study identified a novel role of Sulf-2 in TNF-α signaling and the activation of RA synoviocytes, providing the rationale for evaluating the therapeutic targeting of Sulf-2 in preclinical models of RA.
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