Targeting extracellular CIRP with an X-aptamer shows therapeutic potential in acute pancreatitis

Severe acute pancreatitis (AP) is associated with a high mortality rate. Cold -inducible RNA binding protein (CIRP) can be released from cells in inflammatory conditions and extracellular CIRP acts as a damage-associated molecular pattern. This study aims to explore the role of CIRP in the pathogenesis of AP and evaluate the therapeutic potential of targeting extracellular CIRP with X-aptamers. Our results showed that serum CIRP concentrations were significantly increased in AP mice. Recombinant CIRP triggered mitochondrial injury and ER stress in pancreatic acinar cells. CIRP-/- mice suffered less severe pancreatic injury and inflammatory responses. Using a bead-based X-aptamer library, we identified an X-aptamer that specifically binds to CIRP (XA-CIRP). Structurally, XA-CIRP blocked the interaction between CIRP and TLR4. Functionally, it reduced CIRP-induced pancreatic acinar cell injury in vitro and L-arginine-induced pancreatic injury and inflammation in vivo. Thus, targeting extracellular CIRP with X-aptamers may be a promising strat-egy to treat AP.

Automated summary

This study investigates the role of CIRP in the pathogenesis of severe acute pancreatitis (AP) and explores the therapeutic potential of targeting extracellular CIRP with X-aptamers. The results indicate that serum CIRP concentrations are elevated in AP mice. Recombinant CIRP induces mitochondrial injury and ER stress in pancreatic acinar cells. CIRP-deficient mice exhibit less severe pancreatic injury and inflammatory responses. By employing a bead-based X-aptamer library, a specific X-aptamer that binds to CIRP (XA-CIRP) is identified. Structurally, XA-CIRP inhibits the interaction between CIRP and TLR4. Functionally, it attenuates CIRP-induced pancreatic acinar cell injury in vitro and L-arginine-induced pancreatic injury and inflammation in vivo. Therefore, targeting extracellular CIRP with X-aptamers could be a promising strategy for treating AP.