Identifying cathepsin B as a key regulator of programmed cell death in acute pancreatitis

  • Int Immunopharmacol. 2026 Jul 1:180:116680. doi: 10.1016/j.intimp.2026.116680.
Xiaozhou Xie  1 ,  Yuchen Jia  1 ,  Zheng Wang  1 ,  Haoyu Zhang  1 ,  Jiongdi Lu  1 ,  Feng Cao  1 ,  Fei Li  2
Affiliations
  • 1. Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, China.
  • 2. Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, China. Electronic address: [email protected].
PMID: 42044578 DOI: 10.1016/j.intimp.2026.116680
Abstract

Acute pancreatitis (AP) lacks effective therapies, and excessive programmed cell death (PCD) drives its pathogenesis. This study identified Cathepsin B (CTSB) as a core PCD regulator in AP via bioinformatics and animal experiments. Gene Expression Omnibus (GEO) datasets were analyzed with differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning algorithms, screening CTSB as a hub gene with high diagnostic value and enrichment in PCD/inflammatory pathways. Cerulein-induced AP mice showed activated multiple PCD pathways and elevated cytoplasmic CTSB. CTSB inhibition by CA-074 Me alleviated pancreatic inflammation and injury, reduced inflammatory cytokines, and mitigated Apoptosis, restored autophagic flux, and suppressed Necroptosis, Ferroptosis, Pyroptosis in AP tissues. CTSB is a central regulator of PCD in AP, serving as a promising therapeutic target for AP by modulating diverse PCD modalities.

Keywords
Acute pancreatitis; Cathepsin B; Machine learning; Programmed cell death; WGCNA.
Products