Department of Pharmacology, Yonsei University College of Medicine, Seoul 120-752, Korea.
Korean J Physiol Pharmacol. 2009 Dec;13(6):409-16. doi: 10.4196/kjpp.2009.13.6.409. Epub 2009 Dec 31.
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.
急性胰腺炎是一种与消化酶过早激活相关的多因素疾病。胰腺腺泡细胞中表达的基因决定了疾病的严重程度。本研究通过使用 Cerulein 作为急性胰腺炎的体外模型，确定了胰腺腺泡细胞中差异表达的基因。用 10(-8) M Cerulein 刺激胰腺腺泡 AR42J 细胞 4 小时，使用包含 4000 个大鼠基因的 cDNA 微阵列鉴定改变表达的基因，并通过实时 PCR 进行验证。这些基因在 Cerulein 作用下表达增加 2.5 倍或更高：胆石素、鸟苷酸环化酶、肌球蛋白轻链激酶 2、组织蛋白酶 C、孕激素诱导蛋白和胰蛋白酶 2。Stathin 1 和核糖体蛋白 S13 的表达降低 2.5 倍或更高。实时 PCR 分析显示这些基因随时间的变化。使用针对鸟苷酸环化酶、肌球蛋白轻链激酶 2 和组织蛋白酶 C 的商业上可获得的抗体，通过 Western blot 观察到这些蛋白质随时间的增加。因此，增殖、分化、细胞骨架排列、酶活性和分泌的紊乱可能是急性胰腺炎的潜在机制。
