Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
Pancreas. 2010 Apr;39(3):385-91. doi: 10.1097/MPA.0b013e3181bb9603.
We examined the effect of the overexpression of Smad6 on pancreatic fibrosis after chronic pancreatic injury.
Chronic pancreatic injury was induced in transgenic mice overexpressing Smad6 (Tg mice) in acini and wild-type (Wt) mice by 3 episodes of acute pancreatitis per week for 1 to 4 consecutive weeks. Acute pancreatitis was elicited by 6 intraperitoneal injections of caerulein (Cn) at 50 microg/kg of body weight at hourly intervals. Pancreatic fibrosis was evaluated by histological examination and hydroxyproline content before and 1, 2, 3, and 4 weeks of repetitive episodes of Cn-induced acute pancreatitis. We further determined transforming growth factor beta1 (TGF-beta1) messenger RNA expression and trypsin activity in the pancreas.
After repetitive episodes of acute pancreatitis, pancreatic fibrosis in Tg mice was significantly severer than that in Wt mice at all time points (weeks 1-4). The expression of TGF-beta1 messenger RNA and the activity of trypsin in the pancreas in the Tg mice were significantly high compared with those in the Wt mice at all corresponding time points after repetitive episodes of acute pancreatitis.
These results demonstrated that overexpression of Smad6 in acini enhanced the development of pancreatic fibrosis after chronic pancreatic injury.
研究 Smad6 过表达对慢性胰腺损伤后胰腺纤维化的影响。
通过每周一次连续 4 周给予胰蛋白酶原激活肽（6 次腹腔注射，每次 50μg/kg 体重，间隔 1 小时）的方法诱导 Smad6 过表达转基因鼠（Tg 鼠）和野生型鼠（Wt 鼠）发生慢性胰腺损伤。通过组织学检查和羟脯氨酸含量评估胰腺纤维化，在反复给予胰蛋白酶原激活肽诱导的急性胰腺炎前、后 1、2、3、4 周进行评估。进一步测定胰腺转化生长因子β1（TGF-β1）mRNA 表达和胰蛋白酶活性。
在反复给予急性胰腺炎后，Tg 鼠的胰腺纤维化在所有时间点（1-4 周）均明显比 Wt 鼠严重。在反复给予急性胰腺炎后所有相应时间点，Tg 鼠的 TGF-β1 mRNA 表达和胰腺胰蛋白酶活性均明显高于 Wt 鼠。
这些结果表明，腺泡细胞中 Smad6 的过表达增强了慢性胰腺损伤后胰腺纤维化的发生。
