Altered Gene Expression in Cerulein-Stimulated Pancreatic Acinar Cells: Pathologic Mechanism of Acute Pancreatitis.
10.4196/kjpp.2009.13.6.409
- Author:
Ji Hoon YU
1
;
Joo Weon LIM
;
Hyeyoung KIM
Author Information
1. Department of Pharmacology, Yonsei University College of Medicine, Seoul 120-752, Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
Cerulein;
Pancreatitis;
Acinar cells;
DNA microarray
- MeSH:
Acinar Cells;
Animals;
Antibodies;
Blotting, Western;
Caerulein;
Cathepsin C;
Cytoskeleton;
Gene Expression;
Guanylate Cyclase;
Lithostathine;
Myosin-Light-Chain Kinase;
Oligonucleotide Array Sequence Analysis;
Pancreatitis;
Proteins;
Rats;
Real-Time Polymerase Chain Reaction;
Ribosomal Proteins;
Trypsin
- From:The Korean Journal of Physiology and Pharmacology
2009;13(6):409-416
- CountryRepublic of Korea
- Language:English
-
Abstract:
Acute pancreatitis is a multifactorial disease associated with the premature activation of digestive enzymes. The genes expressed in pancreatic acinar cells determine the severity of the disease. The present study determined the differentially expressed genes in pancreatic acinar cells treated with cerulein as an in vitro model of acute pancreatitis. Pancreatic acinar AR42J cells were stimulated with 10(-8) M cerulein for 4 h, and genes with altered expression were identified using a cDNA microarray for 4,000 rat genes and validated by real-time PCR. These genes showed a 2.5-fold or higher increase with cerulein: lithostatin, guanylate cyclase, myosin light chain kinase 2, cathepsin C, progestin-induced protein, and pancreatic trypsin 2. Stathin 1 and ribosomal protein S13 showed a 2.5-fold or higher decreases in expression. Real-time PCR analysis showed time-dependent alterations of these genes. Using commercially available antibodies specific for guanylate cyclase, myosin light chain kinase 2, and cathepsin C, a time-dependent increase in these proteins were observed by Western blotting. Thus, disturbances in proliferation, differentiation, cytoskeleton arrangement, enzyme activity, and secretion may be underlying mechanisms of acute pancreatitis.
