Murtaugh L Charles, Keefe Matthew D
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84112; email:
Annu Rev Physiol. 2015;77:229-49. doi: 10.1146/annurev-physiol-021014-071727. Epub 2014 Oct 24.
Pancreatitis is caused by inflammatory injury to the exocrine pancreas, from which both humans and animal models appear to recover via regeneration of digestive enzyme-producing acinar cells. This regenerative process involves transient phases of inflammation, metaplasia, and redifferentiation, driven by cell-cell interactions between acinar cells, leukocytes, and resident fibroblasts. The NFκB signaling pathway is a critical determinant of pancreatic inflammation and metaplasia, whereas a number of developmental signals and transcription factors are devoted to promoting acinar redifferentiation after injury. Imbalances between these proinflammatory and prodifferentiation pathways contribute to chronic pancreatitis, characterized by persistent inflammation, fibrosis, and acinar dedifferentiation. Loss of acinar cell differentiation also drives pancreatic cancer initiation, providing a mechanistic link between pancreatitis and cancer risk. Unraveling the molecular bases of exocrine regeneration may identify new therapeutic targets for treatment and prevention of both of these deadly diseases.
胰腺炎是由外分泌胰腺的炎症性损伤引起的，人类和动物模型似乎都能通过产生消化酶的腺泡细胞再生而恢复。这个再生过程涉及炎症、化生和再分化的短暂阶段，由腺泡细胞、白细胞和驻留成纤维细胞之间的细胞间相互作用驱动。NFκB信号通路是胰腺炎症和化生的关键决定因素，而一些发育信号和转录因子则致力于促进损伤后腺泡细胞的再分化。这些促炎和促分化途径之间的失衡会导致慢性胰腺炎，其特征是持续的炎症、纤维化和腺泡细胞去分化。腺泡细胞分化的丧失也会引发胰腺癌，这为胰腺炎和癌症风险之间提供了一个机制联系。阐明外分泌腺再生的分子基础可能会为治疗和预防这两种致命疾病找到新的治疗靶点。
