Ishiwata Toshiyuki, Kudo Mitsuhiro, Onda Munehiko, Fujii Takenori, Teduka Kiyoshi, Suzuki Taeko, Korc Murray, Naito Zenya
Department of Integrative Pathology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Pancreas. 2006 May;32(4):360-8. doi: 10.1097/01.mpa.0000220860.01120.21.
Nestin is a stem cell marker originally described as an intermediate filament protein expressed in neuroepithelial stem cells. In the pancreas, a small number of nestin-expressing cells, which are believed to represent either stem cells or progenitor cells, are known to be present in islets, as well as in some stellate cells, pericytes, and endothelial cells. We monitored pancreatic nestin expression to delineate the location of stem cells/progenitor cells in the pancreas after L-arginine-induced pancreatitis.
Male Wistar rats received 2 intraperitoneal injections of L-arginine, each consisting of 250 mg/100 g of body weight, and were killed 3, 6, and 12 hours and 1, 4, 7, and 14 days later.
Serum amylase and lipase levels increased after L-arginine injection, maximal levels occurring at 3 and 12 hours postinjection, respectively. Six hours after L-arginine injection, interstitial edema was observed in the pancreas, whereas on day 4 postinjection, there was severe pancreatic necrosis. Neovascularization and ductal-ductular proliferation were also present in the pancreas. Immunohistochemical analysis revealed increased Ki-67 labeling in acinar cells and capillary endothelial cells. Immunoblotting using antinestin antibody revealed increased nestin expression after L-arginine injection. In the control rat pancreas, nestin immunoreactivity was detected in a few capillary endothelial cells in some islets. After L-arginine injection, nestin was expressed in proliferating capillary endothelial cells, in stellate cells surrounding ductular structures and in submesothelial cells.
Transient nestin expression occurs in specific cell types during the proliferative stage after recovery from L-arginine-induced pancreatitis and may represent the contribution of stem cells and/or progenitor cells to the regenerative capacity of the pancreas.
巢蛋白是一种干细胞标志物，最初被描述为在神经上皮干细胞中表达的中间丝蛋白。在胰腺中，已知胰岛以及一些星状细胞、周细胞和内皮细胞中存在少量表达巢蛋白的细胞，这些细胞被认为代表干细胞或祖细胞。我们监测胰腺巢蛋白的表达，以描绘L-精氨酸诱导的胰腺炎后胰腺中干细胞/祖细胞的位置。
雄性Wistar大鼠腹腔注射2次L-精氨酸，每次剂量为250mg/100g体重，分别在注射后3、6和12小时以及1、4、7和14天处死大鼠。
注射L-精氨酸后血清淀粉酶和脂肪酶水平升高，最高水平分别出现在注射后3小时和12小时。注射L-精氨酸6小时后，胰腺出现间质水肿，而在注射后第4天，出现严重的胰腺坏死。胰腺中还存在新生血管形成和导管-小导管增生。免疫组织化学分析显示腺泡细胞和毛细血管内皮细胞中Ki-67标记增加。使用抗巢蛋白抗体进行免疫印迹分析显示，注射L-精氨酸后巢蛋白表达增加。在对照大鼠胰腺中，在一些胰岛的少数毛细血管内皮细胞中检测到巢蛋白免疫反应性。注射L-精氨酸后，巢蛋白在增殖的毛细血管内皮细胞、围绕小导管结构的星状细胞和间皮下细胞中表达。
在从L-精氨酸诱导的胰腺炎恢复后的增殖阶段，特定细胞类型中出现短暂的巢蛋白表达，这可能代表干细胞和/或祖细胞对胰腺再生能力的贡献。
