Regeneration and repair of the exocrine pancreas

Annu Rev Physiol. 2015;77:229-49. doi: 10.1146/annurev-physiol-021014-071727. Epub 2014 Oct 24.

Abstract

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.

Keywords: acinar cell; caerulein; cerulein; differentiation; inflammation; metaplasia; pancreatitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acinar Cells / cytology*
  • Acinar Cells / physiology*
  • Animals
  • Cell Differentiation / physiology
  • Disease Models, Animal
  • Humans
  • Pancreas, Exocrine / cytology
  • Pancreas, Exocrine / physiology*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / physiopathology
  • Pancreatitis / pathology
  • Pancreatitis / physiopathology
  • Regeneration / physiology*
  • Signal Transduction / physiology