Knockdown of Galectin-9 alleviates rheumatoid arthritis through suppressing TNF-α-induced activation of fibroblast-like synoviocytes

Jia, Qian; Che, Qincheng; Zhang, Xiaoyu; Chen, Jie; Ren, Chunfeng; Wu, Yunpeng; Liang, Weiqiang; Zhang, Xiaojie; Li, Yanshan; Li, Zunzhong; Zhang, Zhenchun; Shu, Qiang

doi:10.1016/j.bcp.2023.115994

Cited by 2 publications

(1 citation statement)

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“…Endogenous Gal-9 can protect against apoptosis and enhance viability of synovial fibroblast in patients with RA ( 29 ). Knockdown of Gal-9 alleviates the progression of arthritis in a collagen-induced arthritis (CIA) mouse model through the PI3K/AKT/mTOR pathway ( 31 ). In contrast, exogenous Gal-9 preferentially induces apoptosis and suppresses synovial fibroblast proliferation in patients with RA ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Galectin-9 as an indicator of functional limitations and radiographic joint damage in patients with rheumatoid arthritis

Guo,

Ai,

Jia

et al. 2024

Front. Immunol.

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BackgroundPrevious studies have revealed that Galectin-9 (Gal-9) acts as an apoptosis modulator in autoimmunity and rheumatic inflammation. In the present study, we investigated the potential role of Gal-9 as a biomarker in patients with rheumatoid arthritis (RA), especially as an indicator of functional limitations and radiographic joint damage.MethodsA total of 146 patients with RA and 52 age- and sex-matched healthy controls were included in this study. Clinical data including disease activity, physical function, and radiographic joint damage were assessed. Functional limitation was defined as the Stanford Health Assessment Questionnaire (HAQ) disability index >1. Subjects with joint erosion >0 or joint space narrowing >0 were considered to have radiographic joint damage. Serum Gal-9 levels were detected by an enzyme-linked immunosorbent assay. Univariate and multivariate logistic regression analysis were used to evaluate the association between Gal-9 and high disease activity and functional limitations, and a prediction model was established to construct predictive nomograms.ResultsSerum levels of Gal-9 were significantly increased in patients with RA compared to those in healthy controls (median 13.1 ng/mL vs. 7.6 ng/mL). Patients with RA who were older (>65 years), had a longer disease duration (>5 years), longer morning stiffness (>60mins), elevated serum erythrocyte sedimentation rate and C-reactive protein, and difficult-to-treat RA had significantly higher Gal-9 levels than those in the corresponding control subgroups (all p <0.05). Patients with RA were divided into two subgroups according to the cut-off value of Gal-9 of 11.6 ng/mL. Patients with RA with Gal-9 >11.6 ng/mL had a significantly higher core clinical disease activity index, HAQ scores, Sharp/van der Heijde modified Sharp scores, as well as a higher percentage of advanced joint damage (all p<0.05) than patients with Gal-9 ≤11.6 ng/mL. Accordingly, patients with RA presenting either functional limitations or radiographic joint damage had significantly higher serum Gal-9 levels than those without (both p <0.05). Furthermore, multivariate logistic regression analysis showed that a serum level of Gal-9 >11.6 ng/mL was an independent risk factor for high disease activity (OR=3.138, 95% CI 1.150–8.567, p=0.026) and presence of functional limitations (OR=2.455, 95% CI 1.017–5.926, p=0.046), respectively.ConclusionGal-9 could be considered as a potential indicator in patients with RA, especially with respect to functional limitations and joint damage.

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Section: Discussionmentioning

confidence: 99%

Galectin-9 as an indicator of functional limitations and radiographic joint damage in patients with rheumatoid arthritis

Guo,

Ai,

Jia

et al. 2024

Front. Immunol.

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The regulating role of galectin-9 in immune cell populations

Cao,

Leng,

et al. 2024

Front. Pharmacol.

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Galectin-9 (gal-9) is a protein that belongs to the galectin family. Gal-9 is expressed in cells of the innate and adaptive immune system, including lymphocytes, dendritic cells, giant salivary cells, eosinophils and T cells, etc. In different immune cells, the role of gal-9 is different. Gal-9 can induce the proliferation and activation of immune cells, and also promote the apoptosis of immune cells. This effect of gal-9 affects the occurrence and development of a variety of immune-related diseases, such as the invasion of pathogenic microorganisms, immune escape of tumor cells, and inflammatory response. Thus, understanding the biological roles of gal-9 in innate and adaptive immunity may be essential for autoimmune diseases treatment and diagnosis to improve patient quality of life. In this review, we aim to summarize current research on the regulatory roles of gal-9 in human immune system and potential inducers and inhibitors of gal-9, which may provide new strategies for immune diseases therapies.

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Knockdown of Galectin-9 alleviates rheumatoid arthritis through suppressing TNF-α-induced activation of fibroblast-like synoviocytes

Cited by 2 publications

References 61 publications

Galectin-9 as an indicator of functional limitations and radiographic joint damage in patients with rheumatoid arthritis

Galectin-9 as an indicator of functional limitations and radiographic joint damage in patients with rheumatoid arthritis

The regulating role of galectin-9 in immune cell populations

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