| نویسندگان | Farghadan M, Zavaran-Hosseini A, Farhadi E, Sharafat Vaziri A, Tahmasebi M, Jamshidi A and Mahmoudi M |
|---|---|
| همایش | ICIA 2023 16th International Congress of Immunology |
| تاریخ برگزاری همایش | 27-29 April 2023 |
| محل برگزاری همایش | Tehran, Iran |
| نوع ارائه | سخنرانی |
| سطح همایش | بین المللی |
چکیده مقاله
Background: Fibroblast-like synoviocytes (FLSs) play a key role in the pathogenesis of rheumatoid arthritis (RA). Endoplasmic reticulum (ER) stress and dysregulation of unfolded protein response (UPR) is involved in resistance to apoptosis of RA-FLSs. Given the role of miR-211 in ER stress-induced apoptosis, we investigated the effect of miR-211-5p overexpression on PERK branch of ER stress and apoptosis related genes in RA-FLSs.
Methods: After FLSs isolation from synovial tissues of trauma and RA patients, phenotype characterization of the cells was accomplished by immunofluorescence staining and flow cytometry. 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 treated RA-FLSs. Afterward, miR-211-5p and mRNA levels of the studied genes were evaluated in thapsigargin treated RA-FLSs following miR-211-5p overexpression.
Results: The expression of miR-211-5p, PERK, BAX, and BCL2 showed no differences between RA and trauma FLSs. However, the expression of ATF4 and BCL-XL showed a significant increase in trauma compared to RA-FLSs. In addition, the levels of CHOP and MCL1 indicated a significant increase in RA-FLSs compared to trauma. Thapsigargin 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, thapsigargin treatment following miR-211-5p overexpression in RA-FLSs showed a significant increase in levels of miR-211-5p with no change on the expression of CHOP and apoptotic genes.
Conclusion: Based on the results, it seems that there is ER stress in RA and trauma FLSs. In addition, stimulation of ER stress in RA-FLSs and overexpression of miR-211-5p in stimulated RA-FLSs did not alter the expression of selected genes in apoptosis regulation. However, more investigations are necessary to determine the ER stress role in apoptosis regulation in RA-FLSs.
Keywords: ER stress, Fibroblast-like synoviocytes (FLSs), miR-211-5p, Rheumatoid arthritis (RA)