Drug screening and identification of key candidate genes and pathways of rheumatoid arthritis

Shi,Yu‑Quan; Qi,Wu‑Fang; Kong,Chun‑Yu

doi:10.3892/mmr.2020.11168

Drug screening and identification of key candidate genes and pathways of rheumatoid arthritis

Authors:
- Yu‑Quan Shi
- Wu‑Fang Qi
- Chun‑Yu Kong
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Affiliations: Department of Rheumatology and Immunology, Tianjin First Central Hospital, Tianjin 300192, P.R. China
Published online on: May 21, 2020 https://doi.org/10.3892/mmr.2020.11168
Pages: 986-996
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Rheumatoid arthritis (RA), which normally manifests as a multi‑joint inflammatory reaction, is a common immunological disease in clinical practice. However, the pathogenesis of RA has not yet been fully elucidated. Rituximab (RTX) is an effective drug in the treatment of RA, however its therapeutic efficacy and mechanism of action require further investigation. Thus, the present study aimed to screen the candidate key regulatory genes and explain the potential mechanisms of RA. Gene chips of RA and normal joint tissues were analyzed and, gene chips of RTX before and after treatment were investigated. In the present study, strong evidence supporting the pathogenesis of RA and mechanism of action of RTX were also revealed. Differentially expressed genes (DEGs) were analyzed using the limma package of RStudio software. A total of 1,150 DEGs were detected in RA compared with normal joint tissues. The upregulated genes were enriched in ‘interleukin‑12 production’, ‘I‑κB kinase/NF‑κB signaling’, ‘regulation of cytokine production involved in immune response’ and ‘cytokine metabolic process’. Functional enrichment analysis showed that RTX was primarily involved in the inhibition of ‘adaptive immune response’, ‘B cell activation involved in immune response’ and ‘immune effector process’. Subsequently, leukocyte immunoglobulin‑like receptor subfamily B member 1 (LILRB1), a hub gene with high connectivity degree, was selected, and traditional Chinese medicine libraries were molecularly screened according to the structure of the LILRB1 protein. The results indicated that kaempferol 3‑O‑β‑D‑glucosyl‑(1→2)‑β‑D‑glucoside exhibited the highest docking score. In the present study, the DEGs and their biological functions in RA and the pharmacological mechanism of RTX action were determined. Taken together, the results suggested that LILRB1 may be used as a molecular target for RA treatment, and kaempferol 3‑O‑β‑D‑glucosyl‑(1→2)‑β‑D‑glucoside may inhibit the pathological process of RA.

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