Caerulein-induced pancreatitis augments the expression and phosphorylation of collapsin response mediator protein 4

J Hepatobiliary Pancreat Sci. 2016 Jul;23(7):422-31. doi: 10.1002/jhbp.361. Epub 2016 Jun 12.

Abstract

Background: Chronic pancreatitis is a significant risk factor for pancreatic cancer. Previously, we demonstrated that the pancreatic cancer cells show enhanced expression of collapsin response mediator protein 4 (CRMP4) that strongly correlates with severe venous invasion, liver metastasis, and poor prognosis. However, involvement of CRMP4 in acute or chronic pancreatitis remains unknown.

Methods: Acute and chronic pancreatitis mice models were developed by periodic injection of caerulein. The expression levels of CRMP4 and its phosphorylation were examined.

Results: Elevated CRMP4 levels were observed in the infiltrated lymphocytes as well as in the pancreas parenchyma of both acute and chronic pancreatitis. The expression pattern of phosphorylated CRMP4 was similar to that of CRMP4. Cdk5 partially co-localized with the phosphorylated CRMP4.

Conclusions: Pancreatitis induces CRMP4 expression in the pancreas parenchyma and in the infiltrated lymphocytes. Overlapping expression of CRMP4 and Cdk5 may suggest that the Cdk5 is at least, in part, responsible for the phosphorylation of CRMP4. The results suggest that CRMP4 is involved in the inflammatory response in pancreatitis. Understanding the mechanisms of CRMP4 would help us to develop novel therapeutic strategies against acute or chronic pancreatitis, and pancreatic cancer.

Keywords: CRMP4; Cdk5; Pancreatitis; Phosphorylation.

MeSH terms

  • Acute Disease
  • Animals
  • Biopsy, Needle
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • Ceruletide / pharmacology*
  • Chronic Disease
  • Cyclin-Dependent Kinase 5 / genetics
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Mice
  • Nerve Tissue Proteins / genetics*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • Pancreatitis / chemically induced
  • Pancreatitis / pathology*
  • Phosphorylation / genetics
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology*
  • RNA, Small Interfering / analysis*

Substances

  • Dpysl3 protein, mouse
  • Nerve Tissue Proteins
  • RNA, Small Interfering
  • Ceruletide
  • Cyclin-Dependent Kinase 5
  • CDK5 protein, human