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

Liu, Wuming; Bi, Jianbin; Ren, Yifan; Chen, Huan; Zhang, Jia; Wang, Tao; Wang, Mengzhou; Zhang, Lin; Zhao, Junzhou; Wu, Zheng; Lv, Yi; Liu, Bing; Wu, Rongqian

doi:10.1016/j.isci.2023.107043

Cited by 1 publication

(1 citation statement)

References 52 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitochondrial dysfunction and impaired autophagy promote ROS accumulation [ 23 ]. Previously, we demonstrated that extracellular CIRP can directly damage pancreatic acinar cells [ 24 ]. Nonetheless, the precise role of CIRP in the pathogenesis of AP is unclear.…”

Section: Introductionmentioning

confidence: 99%

Blocking CIRP protects against acute pancreatitis by improving mitochondrial function and suppressing pyroptosis in acinar cells

Liu,

Ren,

Wang

et al. 2024

Cell Death Discov.

Self Cite

View full text Add to dashboard Cite

Acute pancreatitis (AP) continues to pose a major challenge as targeted therapeutic interventions are absent. Mitochondrial dysfunction and inflammasome-dependent pyroptosis are involved in the pathogenic mechanisms of AP. CIRP is a stress-response protein and a damage-associated molecular pattern (DAMP) molecule. In our previous studies, we discovered that excessive CIRP can directly damage pancreatic acinar cells. Nonetheless, the precise involvement of CIRP in AP is still unexplored. The primary aim of this study was to examine the potential involvement of CIRP in the development of pyroptosis and mitochondrial dysfunction in AP. To study this, an L-arginine-induced AP mouse model was used. Our results showed that Caspase-1-mediated pyroptosis and mitochondria-derived reactive oxygen species (ROS) were crucial factors in the occurrence of tissue damage and inflammation in AP. A substantial increase in the CIRP serum levels was observed in AP mice. Blocking CIRP by either CIRP gene knockout or systemic administration of C23, a competing inhibitor of CIRP, reduced ROS accumulation and pyroptosis in AP mice. These effects were associated with attenuated pancreatic injury and inflammation. In addition, CIRP-triggered mitochondrial dysfunction, autophagy impairment, and pyroptosis in pancreatic acinar cells were prevented by TAK242, an inhibitor of CIRP receptor TLR4. In conclusion, CIRP can induce mitochondrial dysfunction and pyroptosis in pancreatic acinar cells, and blocking CIRP may be a valuable approach to treating patients with AP.

show abstract

Section: Introductionmentioning

confidence: 99%