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Sestrin2, NFATc1, and NRF2 in PBMCs of patients with ankylosing spondylitis treated with etanercept compared to the new case patients
Zahra Faghhian1 , Jahanbakhsh Asadi1 , Mehrdad Aghaei2 , Masoomeh Gholizadeh1 , Negin Esmaeili3 , Koushan Sineh Sepehr4 , Zahra Hesari1
1- Metabolic Disorders Research Center, Biomedical Research Institute, Golestan University of Medical Sciences, Gorgan, Iran
2- Golestan Rheumatology Research Center, Biomedical Research Institute, Golestan University of Medical Sciences, Gorgan, Iran
3- Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran
4- Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran , koushan2520@gmail.com
Abstract:   (1268 Views)
Background: Ankylosing spondylitis (AS) is an inflammatory autoimmune disease characterized by progressive bone destruction and pathological new bone formation. Sestrin2 is activated in inflammatory and oxidative responses and protects cells from injury. Sestrin inhibits reactive oxygen species (ROS) by activating nuclear factor erythroid 2-related factor 2 (NRF2). Nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), a key regulator of osteoclast differentiation, is induced following stimulation of the receptor activator of nuclear factor kappa-B ligand (RANKL) and promotes bone resorption. Emerging evidence suggests that impaired Sestrin2/NRF2 signaling may lead to increased oxidative stress, thereby enhancing NFATc1 activity and exacerbating bone destruction in AS. This study analyzed the expression of these genes in newly diagnosed AS patients and AS patients receiving etanercept, an anti-tumor necrosis factor (Anti-TNF) drug, compared with a control group.
Methods: The expression levels of Sestrin2, NRF2, and NFATc1 genes were analyzed by real-time PCR in 60 peripheral blood mononuclear cell (PBMC) samples, which were divided into three groups: newly diagnosed AS patients, AS patients receiving etanercept (Etanercept group), and healthy control individuals. Statistical analysis was performed using SPSS version 18 software. A P-value < 0.05 was considered statistically significant.
Results: NRF2 gene expression was increased in the newly diagnosed AS group compared with the control group (P < 0.001). It was also increased in the etanercept group compared with the control group (P < 0.01). The expression levels of the other two genes (SESN2 and NFATc1) in the etanercept group were higher than those in both the newly diagnosed and control groups; however, these differences were not statistically significant (P > 0.05).
Conclusion: The expression levels of genes involved in the regulation of inflammation increased following treatment with etanercept. These results suggest that, in addition to its inhibitory effects on the TNF-α pathway, etanercept may also influence the expression of genes involved in the control of inflammatory processes.
 
Keywords: Nuclear Factor of Activated T-cells, Nuclear Factor E2 Related Factor 2, Sestrins
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Research Article: Research Article | Subject: Biochemistry
Received: 2025/04/12 | Accepted: 2025/06/8
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