MicroRNA-211-5p Overexpression Effect on Endoplasmic Reticulum Stress and Apoptotic Genes in Fibroblast-like Synoviocytes of Rheumatoid Arthritis

Maryam Farghadan; Ahmad Zavaran-Hosseini; Elham Farhadi; Arash Sharafat Vaziri; Mohammad Naghi Tahmasebi; Ahmadreza Jamshidi; Mahdi Mahmoudi

doi:10.18502/ijaai.v21i4.10289

Maryam Farghadan Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Ahmad Zavaran-Hosseini Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Elham Farhadi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Arash Sharafat Vaziri Division of Knee Surgery, Department of Orthopedics, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
Mohammad Naghi Tahmasebi Division of Knee Surgery, Department of Orthopedics, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
Ahmadreza Jamshidi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
Mahdi Mahmoudi Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v21i4.10289

Keywords: Endoplasmic reticulum stress; Fibroblast-like synoviocytes; MiR-211-5p; Rheumatoid arthritis

Abstract

Fibroblast-like synoviocytes (FLSs) play a major role in the pathogenesis of rheumatoid arthritis (RA). Endoplasmic reticulum (ER) stress and dysregulation of unfolded protein response are involved in the resistance to apoptosis of FLSs in RA (RA-FLSs). MicroRNA (MiR)-211 plays an important role in controlling ER stress and apoptotic genes in a PKR-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-dependent manner. We investigated the effect of miR-211-5p overexpression on ER stress and apoptotic genes in RA-FLSs.

FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients. MiR-211-5p and mRNA expression of the selected genes involved in the PERK pathway and apoptosis regulation were measured in RA, trauma, and thapsigargin (Tg)-treated RA-FLSs. Afterward, Tg-treated RA-FLSs following miR-211-5p overexpression were evaluated for miR-211-5p and mRNA levels of the study genes.

The expression of miR-211-5p, PERK, BAX, and BCL2 showed no differences between RA and trauma. However, the expression of ATF4 and BCL-XL showed a significant increase in trauma. In addition, the levels of C/EBP homologous protein (CHOP) and MCL1 indicated a significant increase in RA-FLSs. Tg treatment significantly increased the expression of PERK, ATF4, and CHOP in RA-FLSs with no effect on miR-211-5p, BAX, BCL2, BCL-XL, and MCL1. Furthermore, Tg treatment following miR-211-5p overexpression in RA-FLSs showed a significant increase in levels of miR-211-5p with no changes in apoptotic genes.

MiR-211-5p overexpression in stimulated RA-FLSs did not alter the levels of selected genes involved in apoptosis regulation. However, more investigations are necessary to determine the ER stress role in apoptosis regulation in RA-FLSs.