Transgenic expression of cyclooxygenase-2 in pancreatic acinar cells induces chronic pancreatitis
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 01, 2019
- Source ID
- 10.1152/ajpgi.00096.2018
Entities
People
- Ashley N. Haddock
- Baoan Ji
- Craig D. Logsdon
- Defeng Deng
- Haojie Huang
- Huamin Wang
- Jiaxiang Chen
- Lisi Peng
- Weiqin Lu
- Xianbao Zhan
- Yan Bi
- Yan Y Liu
- Yang Zhang
- Yao Yao
- Zhaoshen Li
Organizations
- Foundation for the National Institutes of Health
- Mayo Clinic
- National Cancer Institute
- National Natural Science Foundation of China
- Naval Medical University
- Stony Brook University
- United States Department of Defense
- University of Texas at Austin