ABSTRACT
AIM: To observe the expressions of early growth response factor-1 (Egr-1) and tissue factor (TF) in rats with cerulein-induced acute pancreatitis and to explore its significance. METHODS: A large dose of cerulein was used to create the experimental acute pancreatitis model in rats. The changes of Egr-1 mRNA and protein in rats were observed during 30 min to 4 h after the treatment and immunohistochemical method was used to observe the localized expression of Egr-1 in tissues. In addition to the mRNA expression of Egr-1 target gene, TF was also observed. A blank control group, and a bombesin-administered group were used for comparison. RESULTS: After the stimulation of a large dose of cerulein, the rats showed typical inflammatory changes of acute pancreatitis. Thirty minutes after the stimulation, the mRNA expression of Egr-1 in the pancreatic tissue reached its peak and then declined, while the expression of Egr-1 protein reached its peak 2 h after the stimulation. Histologically, 2 h after the stimulation, almost all pancreatic acinar cells had the expression of Egr-1 protein, which was focused in the nuclei. The mRNA expression of TF occurred 1 h after the stimulation and gradually increased within 4 h. However, a large dose of bombesin only stimulated the pancreatic tissue to produce a little mRNA expression of Egr-1 and no mRNA expression of Egr-1 protein and TF. CONCLUSION: Egr-1 as a pro-inflammatory transcription factor may play an important role in the pathogenesis of acute pancreatitis by modulating the expression of TF.
Subject(s)
DNA-Binding Proteins/genetics , Immediate-Early Proteins/genetics , Pancreatitis/physiopathology , Transcription Factors/genetics , Acute Disease , Animals , Ceruletide , DNA-Binding Proteins/metabolism , Disease Models, Animal , Early Growth Response Protein 1 , Gene Expression , Immediate-Early Proteins/metabolism , Male , Pancreatitis/chemically induced , Pancreatitis/pathology , Rats , Rats, Wistar , Thromboplastin/genetics , Transcription Factors/metabolismABSTRACT
OBJECTIVE: To observe the expressions of early growth response 1 (Egr-1) and tissue factor (TF) in rat tissues of acute pancreatitis induced by caerulein and to explore their significance. METHODS: Pancreatitis was induced in rats by high-dose intraabdominal caerulein injection. The changes of Egr-1 mRNA and protein in pancreas were measured by quantitative PCR and Western blotting, and the localization of Egr-1 protein in acinar cells was visualized by immunohistochemistry. TF mRNA levels were also measured by quantitative PCR. High-dose bombesin-stimulated rats served as the negative control. RESULTS: Egr-1 mRNA was rapidly increased in the pancreas of rats stimulated by high-dose cearulein, and reached the peak level 30 min after the stimulation, whereas band for peak Egr-1 protein level was visualized by Western blotting till 2 h after stimulation. Immunohistochemistry showed that almost every acinar cell in the pancreas was Egr-1-positive, especially in the nucleus. In line with Egr-1 activation, TF mRNA was detected 1 h after the stimulation and increased steadily within the initial 4 h. Only a small quantity of Egr-1 mRNA expression was observed in bombesin-stimulated rats, in which no Egr-1 protein or TF mRNA were detected. CONCLUSION: Egr-1 mRNA and protein were up-regulated in the early stage of pancreatitis. Egr-1, as a pro-inflammatory transcriptional factor, probably plays an important role in the initiation of acute pancreatitis, and its action might be partially mediated through the up-regulation of TF expression.