Chronic pancreatitis in mice by treatment with choline-deficient ethionine-supplemented diet.
Although chronic pancreatitis is a risk factor for pancreatic ductal adenocarcinoma (PDA), the relationship between chronic pancreatitis and PDA remains obscure. A critical obstacle to understanding the role of chronic pancreatitis is the lack of animal models. To develop one such model, mice were fed long-term with a choline deficient ethionine-supplemented (CDE) diet. Histological evaluation revealed that chronic pancreatitis, characterized by acinar atrophy, fibrosis and well-developed tubular complexes (TCs), was observed after 24 weeks of CDE diet treatment. Furthermore, expression of epidermal growth factor receptor (EGFR) and its ligands; serine protease inhibitor Kazal type 3 (Spink3) and transforming growth factor alpha (TGF alpha) and activation of K-Ras (GTP-Ras formation), which are frequently observed in human PDA, were indeed observed in parallel with TCs formation. Neoplastic lesions were not found after 54 weeks of treatment, suggesting that a continuation of CDE diet or another insult is required for the development of PDA.
Ida
Satoshi
S
Insitute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
Ohmuraya
Masaki
M
Hirota
Masahiko
M
Ozaki
Nobuyuki
N
Hiramatsu
Sayaka
S
Uehara
Hitoshi
H
Takamori
Hiroshi
H
Araki
Kimi
K
Baba
Hideo
H
Yamamura
Ken-ichi
K
D000681:Amylases / Q000097:blood; D000821:Animal Feed / Q000009:adverse effects*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002796:Choline Deficiency / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000378:metabolism; D005001:Ethionine / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000209:etiology* / Q000473:pathology; D029584:Prostatic Secretory Proteins / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014359:Trypsin Inhibitor, Kazal Pancreatic; D018631:ras Proteins / Q000378:metabolism
D015415:Biomarkers; D006023:Glycoproteins; D029584:Prostatic Secretory Proteins; C487134:Spink1 protein, mouse; D016211:Transforming Growth Factor alpha; D014359:Trypsin Inhibitor, Kazal Pancreatic; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D000681:Amylases; D018631:ras Proteins; D005001:Ethionine