Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes

Abstract

Background: Rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLSs) play important roles in pathogenesis of rheumatoid arthritis (RA). Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, is a potentially effective therapy for RA, but its underlying mechanism is unclear. In this study, we explore the effects of WJT on human RA-FLSs and the underlying molecular mechanism. Methods: The major components of WJT were determined using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Cell proliferative ability was evaluated by CCK-8, colony formation assay, and EdU incorporation assay. Cell apoptotic capacity was examined by caspase-3 and caspase-9 activity test. Protein levels of Bax and Bcl-2 were investigated by western blotting. High-throughput sequencing and bioinformatics analysis were conducted to screen and identify targeted genes, followed by identification by qRT-PCR and western blotting. Results: In this study, we have identified 346 compounds in WJT. Our results showed that WJT inhibited the RA-FLSs proliferation, and promoted apoptosis in a dose-and time-dependent manner. More importantly, 184 differentially expressed genes (DEGs) has been screened after WJT treatment based on DEGSeq2 and 278 DEGs was identified by DEGSeq2 combined with WGCNA. Then, 10 hub genes were identified based on two different analyses, while the expression levels of only SMC3, THOC1, BUB1, and STAG2 were decreased after WJT treatment, which was identical to the sequencing profiles. Conclusions: WJT exerted its anti-proliferation and pro-apoptosis effects possibly through suppressing the expression of SMC3, THOC1, BUB1, and STAG2 in RA-FLSs. Thus, therapeutics targeting these genes may be a promising strategy for rescuing RA.

Analysis and Experimental Validation of Rheumatoid Arthritis Innate Immunity Gene CYFIP2 and Pan-Cancer

“…Meanwhile, the emerging weighted gene co-expression network analysis (WGCNA) has gradually been used in the association between diseases along with related phenotypes and clusters (modules) of highly corrected genes ( 15 ). Several studies have illustrated the effects of the hub gene and underlying molecular mechanisms in RA patients through WGCNA analysis ( 25 , 26 ). While comprehensive immune infiltration and related pathways are still deficient.…”

Screening of potentially active compounds against rheumatoid arthritis in the Juan-Bi decoction using systems pharmacology and animal experiments

“…These cascading effects ultimately lead to joint damage and physical disability ( Mueller et al, 2021 ). There are multiple immune function-related pathways correlated with RA that include the JAK/STAT signaling pathway, the NF-κB signaling pathway, the AMPK signaling pathway, and the TLR signaling pathway ( Li et al, 2019a ; Cheng et al, 2020 ; Li et al, 2020 ). Contemporary RA treatment for encompass several approaches, such as utilizing composite markers for gauging disease activity, implementing targeted therapy strategies, and employing a range of conventional, biological, and innovative non-biological anti-rheumatic drugs for managing the condition ( Smolen et al, 2016 ).…”

Table1.xlsx

“…These cascading effects ultimately lead to joint damage and physical disability (Mueller et al, 2021). There are multiple immune function-related pathways correlated with RA that include the JAK/STAT signaling pathway, the NF-κB signaling pathway, the AMPK signaling pathway, and the TLR signaling pathway (Li et al, 2019a;Cheng et al, 2020;Li et al, 2020). Contemporary RA treatment for encompass several approaches, such as utilizing composite markers for gauging disease activity, implementing targeted therapy strategies, and employing a range of conventional, biological, and innovative non-biological anti-rheumatic drugs for managing the condition (Smolen et al, 2016).…”