Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Gene Expression Profiling to Unfolded Proteins Response as a Risk Modulator of Patients with Rheumatoid Arthritis.

Version 1 : Received: 15 March 2024 / Approved: 15 March 2024 / Online: 15 March 2024 (14:59:49 CET)

A peer-reviewed article of this Preprint also exists.

Kucharska-Lusina, A.; Skrzypek, M.; Binda, A.; Majsterek, I. Gene Expression Profiling to Unfolded Proteins Response as a Risk Modulator of Patients with Rheumatoid Arthritis. Int. J. Mol. Sci. 2024, 25, 4854. Kucharska-Lusina, A.; Skrzypek, M.; Binda, A.; Majsterek, I. Gene Expression Profiling to Unfolded Proteins Response as a Risk Modulator of Patients with Rheumatoid Arthritis. Int. J. Mol. Sci. 2024, 25, 4854.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that these ER-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including total 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the PERK-UPR associated genes: p-eIF2, BCL-2, PERK, ATF4, BAX were investigated by Real-Time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression of PERK, BCL-2, p-eIF2, ATF4, BAX was found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056 and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors, may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

Keywords

endoplasmic reticulum stress, unfolded protein response, ER-adaptosome, PERK inhibitor, rheumatoid arthritis.

Subject

Medicine and Pharmacology, Medicine and Pharmacology

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