Abstract
OBJECTIVES: Chronic pancreatitis (CP) is characterized by inflammation and fibrosis of the pancreas, leading to pain, parenchymal damage, and loss of exocrine and endocrine function. There are currently no curative therapies; diagnosis remains difficult and aspects of pathogenesis remain unclear. Thus, there is a need to identify novel biomarkers to improve diagnosis and understand pathophysiology. We hypothesize that pancreatic acinar regions contain proteomic signatures relevant to disease processes, including secreted proteins that could be detected in biofluids. METHODS: Acini from pancreata of mice injected with or without caerulein were collected using laser capture microdissection followed by mass spectrometry analysis. This protocol enabled high-throughput analysis that captured altered protein expression throughout the stages of CP. RESULTS: Over 2,900 proteins were identified, whereas 331 were significantly changed ≥ 2-fold by mass spectrometry spectral count analysis. Consistent with pathogenesis, we observed increases in proteins related to fibrosis (e.g., collagen, P<0.001), several proteases (e.g., trypsin 1, P<0.001), and altered expression of proteins associated with diminished pancreas function (e.g., lipase, amylase, P<0.05). In comparison with proteomic data from a public data set of CP patients, a significant correlation was observed between proteomic changes in tissue from both the caerulein model and CP patients (r=0.725, P<0.001). CONCLUSIONS: This study illustrates the ability to characterize proteome changes of acinar cells isolated from pancreata of caerulein-treated mice and demonstrates a relationship between signatures from murine and human CP.
| Original language | English |
|---|---|
| Article number | e89 |
| Journal | Clinical and Translational Gastroenterology |
| Volume | 8 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2017 |
Bibliographical note
Funding Information:Guarantor of the article: Darwin L. Conwell, MD, MS. Specific author contributions: John P. Shapiro: performed experiments, collected and interpreted data, guided direction of project, and assisted in writing of the manuscript. He has approved the final draft submitted. Hannah M. Komar: performed experiments, collected and interpreted data, guided direction of project, and assisted in writing of the manuscript. She has approved the final draft submitted. Baris Hancioglu: Data analysis. He has approved the final draft submitted. Lianbo Yu: Data analysis. He has approved the final draft submitted. Ming Jin: pathologic analysis. She has approved the final draft submitted. Phil A. Hart: guided direction of project and assisted in writing manuscript. He has approved the final draft submitted. Zobeida Cruz-Monserrate: guided direction of project and assisted in writing manuscript. She has approved the final draft submitted. Gregory B. Lesinski: guided direction of project, funded portions of the study, and assisted in writing the manuscript. He has approved the final draft submitted. Darwin L. Conwell: guarantor of the article. Guided direction of project, funded portions of the study, and assisted in writing manuscript. He has approved the final draft submitted. Financial support: This research was supported (to P.A.H. and D.L.C.) by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Cancer Institute (NCI); U01DK108327, P30 CA016058, the National Institute of Allergy and Infectious Diseases (NIAID), 1R21AI124687-01 (to G.B.L.), the National Pancreas Foundation (to G.B.L.), and the Division of Gastroenterology, Hepatology and Nutrition at the Ohio State University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Potential competing interests: None.
Publisher Copyright:
© 2017 the American College of Gastroenterology.
ASJC Scopus subject areas
- Gastroenterology
