Yuxian Shen
Anhui Medical University, China
Title: The role of Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) in inflammatory arthritis
Biography
Biography: Yuxian Shen
Abstract
Inflammation can cause endoplasmic reticulum (ER) stress and therefore activates the unfolded protein response (UPR). ER stress and the consequent UPR have the potential to activate NF-kB. However, the factors mediating the crosstalk between ER stress and the NF-κB pathway remain unclear. Here, we showed that ER stress inducible protein Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) was up-regulated in autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis, and inflammatory disease models. Inflammation caused MANF to relocalize to the nuclei. MANF interacted with the DNA binding domain of p65 through its C-terminal SAP-like domain in the nuclei under the condition of inflammation or ER stress. MANF consequently inhibited p65-mediated transcriptional activation by interfering with the binding of p65 to its target genes promoters. Consistently, MANF suppressed the expressions of NF-κB-dependent target genes and the proliferation of inflammatory synoviocytes. These findings suggest that MANF may be a negative regulator of inflammation and mediate the crosstalk between the NF-κB pathway and ER stress.