Transgenic expression of cyclooxygenase-2 in pancreatic acinar cells induces chronic pancreatitis

Haojie Huang, Jiaxiang Chen, Lisi Peng, Yao Yao, Defeng Deng, Yang Zhang, Yan Liu, Huamin Wang, Zhaoshen Li, Yan Bi, Ashley N. Haddock, Xianbao Zhan, Weiqin Lu, Craig D. Logsdon, Baoan D Ji

Research output: Contribution to journalArticle

Abstract

Replacement of the exocrine parenchyma by fibrous tissue is a main characteristic of chronic pancreatitis. Understanding the mechanisms of pancreatic fibrogenesis is critical for the development of preventive and therapeutic interventions. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme for prostaglandin synthesis, is expressed in patients with chronic pancreatitis. However, it is unknown whether COX-2 can cause chronic pancreatitis. To investigate the roles of pancreatic acinar COX-2 in fibrogenesis and the development of chronic pancreatitis, COX-2 was ectopically expressed specifically in pancreatic acinar cells in transgenic mice. Histopathological changes and expression levels of several profibrogenic factors related to chronic pancreatitis were evaluated. COX-2 was expressed in the pancreas of the transgenic mice, as detected by Western blot analysis. Immunohistochemical staining showed COX-2 was specifically expressed in pancreatic acinar cells. COX-2 expression led to progressive changes in the pancreas, including pancreas megaly, persistent inflammation, collagen deposition, and acinar-to-ductal metaplasia. Quantitative RT-PCR and immunostaining showed that profibrogenic factors were upregulated and pancreatic stellate cells were activated in the COX-2 transgenic mice. Expression of COX-2 in pancreatic acinar cells is sufficient to induce chronic pancreatitis. Targeting this pathway may be valuable in the prevention of chronic pancreatitis. NEW & NOTEWORTHY COX-2 expression is observed in pancreatic tissues of human chronic pancreatitis. In this study, we showed that COX-2 expression caused the development of chronic pancreatitis in transgenic mice, supporting the idea that COX-2 inhibition may be an effective preventive and therapeutic strategy.

Original languageEnglish (US)
Pages (from-to)G179-G186
JournalAmerican journal of physiology. Gastrointestinal and liver physiology
Volume316
Issue number1
DOIs
StatePublished - Jan 1 2019

Keywords

  • chronic inflammation
  • fibrogenesis
  • pancreatic stellate cells
  • prostaglandin

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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  • Cite this

    Huang, H., Chen, J., Peng, L., Yao, Y., Deng, D., Zhang, Y., Liu, Y., Wang, H., Li, Z., Bi, Y., Haddock, A. N., Zhan, X., Lu, W., Logsdon, C. D., & Ji, B. D. (2019). Transgenic expression of cyclooxygenase-2 in pancreatic acinar cells induces chronic pancreatitis. American journal of physiology. Gastrointestinal and liver physiology, 316(1), G179-G186. https://doi.org/10.1152/ajpgi.00096.2018