Abstract
Purpose: Despite recent advances in the diagnosis and treatment of rheumatoid arthritis (RA), this inflammatory disease remains a challenge to patients and physicians. Recent evidence highlights the contribution of endoplasmic reticulum (ER) stress in the pathogenesis and treatment of RA. Herein, we study the expression of the ER stress sensor inositol-requiring enzyme 1α (IRE1α), as well as XBP1 splicing and the regulated IRE1-dependent decay (RIDD), in peripheral blood mononuclear cells (PBMCs) from patients with RA compared with healthy controls. Methods: The PBMCs from blood samples of RA patients and healthy volunteers were isolated by a density gradient centrifugation method using Ficoll. The gene expression levels of GRP78/ Bip, IRE1, XBP1s, micro-RNAs (miRNAs) were evaluated by real-time PCR. Results: The expression of GRP78, IRE1, and XBP1s were increased in PBMCs of RA patients compared with healthy controls. We further show that the RIDD targets (miRNA-17, -34a, -96, and -125b) were downregulated in RA samples. Conclusion: This study can expand our knowledge on the importance of RNase activity of IRE1α in RA and may offer new potentials for developing novel diagnostic and/or therapeutic biomarkers.
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with swelling of synovial joints, systemic pain and progressive disability in movement.[1]
We study the expression of the endoplasmic reticulum (ER) stress sensor inositol-requiring enzyme 1α (IRE1α), as well as X-binding protein 1 (XBP1) splicing and the regulated IRE1-dependent decay (RIDD), in peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA) compared with healthy controls
To determine the functional activation of IRE1/XBP1 axis of the unfolded protein response (UPR), we evaluated the splicing of XBP1 in RA samples (Figure 1C)
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with swelling of synovial joints, systemic pain and progressive disability in movement.[1].
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