TXNDC5 contributes to rheumatoid arthritis by down-regulating IGFBP1 expression

Area of Science:

• Rheumatology
• Molecular Biology
• Endocrinology

Background:

• Rheumatoid arthritis (RA) susceptibility is linked to the TXNDC5 gene, with elevated expression in synovial tissues.
• TXNDC5 is also associated with diabetes and impaired insulin signaling, suggesting a role in metabolic and inflammatory pathways.

Purpose of the Study:

• To investigate the role of TXNDC5 in rheumatoid arthritis (RA) pathogenesis through the insulin signaling pathway.
• To determine if TXNDC5 influences insulin-like growth factor binding protein 1 (IGFBP1) expression and subsequent fibroblast-like cell behavior in RA.

Main Methods:

• Rheumatoid arthritis synovial fibroblast-like cells (RASFs) were treated with anti-TXNDC5 small interfering RNA (siRNA).
• Insulin signaling and resistance pathways were analyzed using RT2 profiler PCR arrays.
• Gene and protein expression of TXNDC5, IGFBP1, and IL-6 were assessed via real-time PCR and Western blot. Cell proliferation, migration, and apoptosis were evaluated.

Main Results:

• Suppression of TXNDC5 in RASFs led to significantly increased IGFBP1 expression.
• Elevated IGFBP1 and reduced IL-6 were observed in the culture medium of TXNDC5-suppressed RASFs.
• Reduced IGFBP1 and altered cell behavior (increased apoptosis, decreased proliferation/migration) were noted in RA synovial tissues and RASFs, with partial restoration upon IGFBP1 modulation.

Conclusions:

• TXNDC5 contributes to abnormal proliferation, migration, and IL-6 production in RASFs by inhibiting IGFBP1 expression.
• Modulating IGFBP1 levels can restore normal cell functions, highlighting its critical role in RA pathogenesis.
• TXNDC5's role in RA may involve the dysregulation of the insulin-like growth factor (IGF) signaling pathway via IGFBP1.