The Novel Synthetic Peptide AESIS-1 Exerts a Preventive Effect on Collagen-Induced Arthritis Mouse Model via STAT3 Suppression

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that is associated with systemic inflammation and results in the destruction of joints and cartilage. The pathogenesis of RA involves a complex inflammatory process resulting from the action of various proinflammatory cytokines and, therefore, many novel therapeutic agents to block cytokines or cytokine-mediated signaling have been developed. Here, we tested the preventive effects of a small peptide, AESIS-1, in a mouse model of collagen-induced arthritis (CIA) with the aim of identifying a novel safe and effective biological for treating RA. This novel peptide significantly suppressed the induction and development of CIA, resulting in the suppression of synovial inflammation and cartilage degradation in vivo. Moreover, AESIS-1 regulated JAK/STAT3-mediated gene expression in vitro. In particular, the gene with the most significant change in expression was suppressor of cytokine signaling 3 (Socs3), which was enhanced 8-fold. Expression of the STAT3-specific inhibitor, Socs3, was obviously enhanced dose-dependently by AESIS-1 at both the mRNA and protein levels, resulting in a significant reduction of STAT3 phosphorylation in splenocytes from severe CIA mice. This indicated that AESIS-1 regulated STAT3 activity by upregulation of SOCS3 expression. Furthermore, IL-17 expression and the frequency of Th17 cells were considerably decreased by AESIS-1 in vivo and in vitro. Collectively, our data suggest that the novel synthetic peptide AESIS-1 could be an effective therapeutic for treating RA via the downregulation of STAT3 signaling.

Network pharmacology and bioinformatics analysis identified essential genes of Jingulian in the treatment of rheumatoid arthritis and COVID-19

“…STAT3 is activated in response to the phosphorylation of various cytokines and growth factors, such as IFN-γ, IL-5, IL-6, and LIF. A previous study reported that the novel synthetic peptide AESIS-1 could be an effective therapeutic for treating RA via the downregulation of STAT3 signaling (25). Therefore, we speculated that Jingulian may directly activate the PI3K pathway and inhibits the molecular function of STAT3 to reduce the inflammatory response.…”

Activation of formyl peptide receptor 1 elicits therapeutic effects against collagen‐induced arthritis

“…First, we examined the effects of WKYMVm, a surrogate agonist for FPRs, on CIA according to a previous report 27 . CIA mice with vehicle showed markedly increased paw thickness and clinical scores from day 26, which were sustained up to 35 days after immunization (Figure 1A).…”

“…First, we examined the effects of WKYMVm, a surrogate agonist for FPRs, on CIA according to a previous report. 27 CIA mice with vehicle showed markedly increased paw thickness and clinical scores from day 26, which were sustained up to 35 days after immunization (Figure 1A ). However, administration of WKYMVm in CIA mice significantly attenuated the clinical signs of CIA, showing decreased paw swelling compared to the vehicle‐treated arthritic group (Figure 1A, B ).…”

AESIS-1, a Rheumatoid Arthritis Therapeutic Peptide, Accelerates Wound Healing by Promoting Fibroblast Migration in a CXCR2-Dependent Manner

“…In previous research, the novel synthetic peptide AESIS-1 had preventive effects on a collagen-induced arthritis (CIA) model in mice, which is the most widely studied model of rheumatoid arthritis [33,34]. To investigate the efficacy of the AESIS-1 peptide on chronic wound repair, a diabetic wound-healing model was used in this study.…”

“…A previous study of the novel 19-amino-acid bioactive peptide AESIS-1 found it to have therapeutic activity for rheumatoid arthritis treatment [33]. Based on several reports of delayed wound-healing side effects common in rheumatoid arthritis patients [1,3] and reports that rheumatoid arthritis therapeutics can accelerate the wound-healing process [4], we conducted a study on the possibility of applying AESIS-1, an anti-RA agent, as a woundrepair therapeutic.…”