November 12, 2014
Notes: Hamoir, Coralie
Deprez, Pierre H
Digestion. 2013;87(4):229-39. doi: 10.1159/000348439. Epub 2013 Jun 4.
Author Address: Hepato-Gastroenterology Department, Cliniques universitaires Saint-Luc, Universite Catholique de Louvain, Brussels, Belgium.
Reference Type: Journal Article
Record Number: 5231Author: Han, S., Englander, E. W., Gomez, G. A., Aronson, J. F., Rastellini, C., Garofalo, R. P., Kolli, D., Quertermous, T., Kundu, R. and Greeley, G. H., Jr.
Title: Pancreatitis activates pancreatic apelin-APJ axis in mice
Journal: Am J Physiol Gastrointest Liver Physiol
Date: Jul 15
Short Title: Pancreatitis activates pancreatic apelin-APJ axis in mice
Alternate Journal: American journal of physiology. Gastrointestinal and liver physiology
ISSN: 1522-1547 (Electronic)
Accession Number: 23681476
Gene Expression Regulation/physiology
Granulocyte Colony-Stimulating Factor/genetics/metabolism
Intercellular Signaling Peptides and Proteins/genetics/*metabolism
Recombinant Fusion Proteins/genetics/metabolism
Abstract: Pancreatitis is classified into acute pancreatitis (AP) and chronic pancreatitis (CP). Apelin, a small regulatory peptide, is the endogenous ligand for the APJ receptor. Apelin and APJ are expressed in the pancreas. The aims of this study were to examine whether apelin influences the inflammatory and fibrosis responses to pancreatitis in mice and to identify mechanisms behind apelin’s activities. Supramaximal cerulein induction of AP or CP caused significant (P < 0.05) elevations in pancreatic apelin and APJ expression. Levels declined during the recovery phases. In apelin gene-knockout mice with pancreatitis, pancreatic neutrophil invasion and myeloperoxidase activity were enhanced significantly, and apelin treatment suppressed both. Apelin exposure reduced CP-induced elevations of extracellular matrix-associated proteins. Apelin inhibited PDGF-simulated connective tissue growth factor production and proliferation of pancreatic stellate cells (PSCs). Serum granulocyte colony-stimulating factor and keratinocyte cytokine levels were higher in apelin gene-knockout than wild-type mice with pancreatitis. Apelin reduced AP- and CP-induced elevations in pancreatic NF-kappaB activation. Together, these findings imply that the pancreatic apelin-APJ system functions to curb the inflammatory and fibrosis responses during pancreatitis. Furthermore, findings suggest that apelin reduces inflammation and fibrosis by reducing neutrophil recruitment and PSC activity. Inhibition of neutrophil invasion may be mediated by reduced keratinocyte cytokine and granulocyte colony-stimulating factor secretion. Apelin-induced reductions in PSC proliferation and connective tissue growth factor production are putative mechanisms underlying apelin’s inhibition of extracellular matrix production. The apelin-associated changes in NF-kappaB binding may be linked to apelin’s regulation of pancreatic inflammatory and fibrosis responses during pancreatitis.