Logo-apb
Adv Pharm Bull. 2019;9(3): 505-509.
doi: 10.15171/apb.2019.060
PMID: 31592115
PMCID: PMC6773928
Scopus ID: 85070448366
  Abstract View: 395
  PDF Download: 307

Short Communication

The Increased RNase Activity of IRE1α in PBMCs from Patients with Rheumatoid Arthritis

Mahdieh Ahmadiany 1,2, Mahshid Alavi-Samani 1,2, Zahra Hashemi 3, Mohammad Amin Moosavi 4 ORCID logo, Marveh Rahmati 1 * ORCID logo

1 Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
2 Department of Biochemistry, Faculty of Advanced Sciences & Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran (IAUPS).
3 Department of Rheumatology, Imam Hossein Teaching Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4 Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran P.O Box 14965/161, Iran.

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.

Keywords: Endoplasmic reticulum stress, Inositol-requiring enzyme 1, IRE1-dependent decay, microRNA, Rheumatoid arthritis
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Submitted: 17 Mar 2019
Revision: 30 May 2019
Accepted: 01 Jun 2019
ePublished: 01 Aug 2019
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