Defined localization of nestin-expressing cells in L-arginine-induced acute pancreatitis
Defined localization of nestin-expressing cells in L-arginine-induced acute pancreatitis
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DOI：
10.1097/01.mpa.0000220860.01120.21
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发表时间：
2006-05-01
期刊：
影响因子：
2.9
通讯作者：
Naito, Zenya
中科院分区：
文献类型：
--
作者：
Ishiwata, Toshiyuki;Kudo, Mitsuhiro;Naito, Zenya
目的：巢蛋白是一种干细胞标志物，最初被描述为神经上皮干细胞中表达的中间丝蛋白。在胰腺中，少量表达巢蛋白的细胞，被认为代表干细胞或祖细胞，已知存在于胰岛，以及一些星状细胞、周细胞和内皮细胞中。我们监测胰腺巢蛋白的表达，以确定l -精氨酸诱导的胰腺炎后胰腺中干细胞/祖细胞的位置。方法：雄性Wistar大鼠2次腹腔注射l -精氨酸，每次250 mg/100 g体重，分别于3、6、12 h和1、4、7、14 d后处死。结果：l -精氨酸注射后血清淀粉酶和脂肪酶水平升高，分别在注射后3小时和12小时达到最高水平。l -精氨酸注射后6小时胰腺间质水肿，注射后第4天出现严重胰腺坏死。胰腺也有新生血管和导管-导管增生。免疫组化分析显示，腺泡细胞和毛细血管内皮细胞中Ki-67标记升高。免疫印迹法显示注射l -精氨酸后巢蛋白表达增加。在对照大鼠胰腺，部分胰岛毛细血管内皮细胞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、导管结构周围的星状细胞和间皮下层细胞中表达。结论：在l -精氨酸诱导的胰腺炎恢复后的增殖阶段，特定类型的细胞中出现了短暂的巢蛋白表达，可能代表了干细胞和/或祖细胞对胰腺再生能力的贡献。
Objective: 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 cell s/progenitor cells in the pancreas after L-arginine-induced pancreatitis.Methods: 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.Results: 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.Conclusions: 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.