TXNDC5 synergizes with HSC70 to exacerbate the inflammatory phenotype of synovial fibroblasts in rheumatoid arthritis through NF-κB signaling.

ABSTRACT: The upregulated expression of thioredoxin domain-containing protein 5 (TXNDC5) is associated with rheumatoid arthritis in patients and model mice. However, the underlying mechanism by which TXNDC5 influences the pathological activation of rheumatoid arthritis synovial fibroblasts (RASFs) remains unknown. In this study, we show that TXNDC5 expression in RASFs and their cytokine production are significantly upregulated in response to LPS, TNF-α and IL-6, but suppressed by transfection with TXNDC5-siRNA. TXNDC5 is further validated as the direct target of NF-κB signaling. Mechanistically, TXNDC5 directly interacts with heat shock cognate 70 protein (HSC70) to sequester it in the cytoplasm, and HSC70 silencing exerts the same effects as TXNDC5 on the biological activity of RASFs (for example,

SUBMITTER: Wang L 

PROVIDER: S-EPMC6123406 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature