HAPLN1 secreted by synovial fibroblasts in rheumatoid arthritis promotes macrophage polarization towards the M1 phenotype.
- Author:
Chenggen LUO
1
;
Kun HUANG
2
;
Xiaoli PAN
3
;
Yong CHEN
3
;
Yanjuan CHEN
3
;
Yunting CHEN
3
;
Mang HE
3
;
Mei TIAN
4
Author Information
1. Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000; Department of Nephrology, Tongren People's Hospital, Tongren 554300, China.
2. Orthopedics Department of Zunyi First People's Hospital, Zunyi 563100, China.
3. Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China.
4. Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China. *Corresponding author, E-mail: 348820517@qq.com.
- Publication Type:Journal Article
- MeSH:
Humans;
Arthritis, Rheumatoid/genetics*;
Macrophages/immunology*;
Fibroblasts/metabolism*;
Phenotype;
Extracellular Matrix Proteins/genetics*;
Proteoglycans/genetics*;
Synovial Membrane/cytology*;
Tumor Necrosis Factor-alpha/genetics*;
Interleukin-1beta/genetics*;
Nitric Oxide Synthase Type II/genetics*;
Cell Differentiation;
Coculture Techniques;
THP-1 Cells
- From:
Chinese Journal of Cellular and Molecular Immunology
2025;41(5):413-419
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of hyaluronic acid and proteoglycan-linked protein 1 (HAPLN1) secreted by synovial fibroblasts (FLS) on the polarization of macrophages (Mϕ) in rheumatoid arthritis (RA). Methods Human monocytic leukemia cells (THP-1) were differentiated into Mϕ, which were subsequently exposed to recombinant HAPLN1 (rHAPLN1). RA-FLS were transfected separately with HAPLN1 overexpression plasmid (HAPLN1OE) or small interfering RNA targeting HAPLN1 (si-HAPLN1), and then co-cultured with Mϕ to establish a co-culture model. The viability of Mϕ was assessed using the CCK-8 assay, and the proportions of pro-inflammatory M1-type and anti-inflammatory M2-type Mϕ were analyzed by flow cytometry. Additionally, the expression levels of inflammatory markers, including interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS), were quantified using quantitative real-time PCR and Western blot analysis. Results The viability of Mϕ was increased in the rHAPLN1 group compared to the control group. Furthermore, both the M1/Mϕ ratio and inflammatory factor levels were elevated in the rHAPLN1 and HAPLN1OE groups. In contrast, the si-HAPLN1 group exhibited a decrease in the M1/Mϕ ratio and inflammatory factor expression. Notably, the introduction of rHAPLN1 in rescue experiments further promoted Mϕ polarization towards the M1 phenotype. Conclusion HAPLN1, secreted by RA fibroblast-like synoviocytes (RA-FLS), enhances Mϕ polarization towards the M1 phenotype.
