Identification and application of pancreatic internal and external progenitor cell having differentiation potency to β-cells

角质形成细胞生长因子（keratinocytegrowthfactor，KGF）是FGF家族的成员，参与细胞生长、分化、粘附、迁移和组织形态发生的调控。此外，据报道，FGF和受体FGFR有助于胰腺的发育。KGF的特异性受体KGFR/FGFR 2-IIIb也被认为是胰腺发育早期的重要分子。我们，集中在KGF和KGFR/FGFR 2-IIIb的表达，应用胰腺切除术模型和急性L-精氨酸-胰腺炎模型的大鼠来仔细检查成人胰腺的再生。我们试图进一步鉴定有助于内分泌和外分泌细胞再生的胰腺祖细胞。大鼠胰腺切除模型1）在胰腺腺泡细胞、分泌管细胞和胰岛内分泌细胞中可见大量Ki 67阳性细胞。Ki 67阳性细胞数在pancr后3天明显增加 关于我们 胰腺切除术后第7天逐渐下降。2)胰腺切除术组胰腺组织中PDX-1阳性细胞数明显多于对照组。这表明胰腺切除术后PDX-1的表达增加。3)KGFR在胰岛α细胞中表达，提示KGF参与了胰岛α细胞的功能分化。L-精氨酸诱导的胰腺炎1）L-精氨酸注射后6小时，在胰腺中观察到间质水肿，而在注射后第4天，有严重的胰腺坏死。2)胰腺中也存在新生血管和导管-导管增生。3)免疫组化分析显示腺泡细胞和毛细血管内皮细胞的Ki-67标记增加。4)使用抗巢蛋白抗体的免疫印迹显示L-精氨酸注射后巢蛋白表达增加。在对照组大鼠胰腺中，巢蛋白免疫反应在一些胰岛的毛细血管内皮细胞中检测到。5)注射L-精氨酸后，巢蛋白表达于增生的毛细血管内皮细胞、小管结构周围的星状细胞和中皮下细胞。结论：瞬时巢蛋白表达发生在特定的细胞类型的增殖阶段后，从L-精氨酸诱导的胰腺炎恢复，并可能代表干细胞和/或祖细胞的胰腺再生能力的贡献。少

Keratinocyte growth factor, KGF, is a member of FGF families that has been known to participate in regulation of cell growth, differentiation, adhesion, migration and the tissue morphogenesis. Furthermore, it is reported that FGF and the receptor FGFR contribute to the development of the pancreas. The specific receptor of KGF, KGFR/FGFR2-IIIb, is also suggested to be an important molecule in the early period of pancreatic development. We, having focused on the expression of KGF and KGFR/FGFR2-IIIb, applied both the pancreatectomy model and the acute L-arginine-pancreatitis model of the rat to scrutinize regeneration of the adult pancreas. We tried further to identify the pancreatic progenitor cells that contribute to regenerate endocrine and exocrine cells.A. Rat pancreatectomy model1) Many Ki67 positive cells were observed in pancreatic acinar cells, excretory ductal cells and endocrine cells of the islet. The number of Ki67 positive cells increased significantly in 3 days after pancr … More eatectomy and decreased gradually in seven days after the pancreatectomy. 2) The PDX-1 positive cells also were observed in significantly large numbers in pancreatectomy group in comparison with control group. This suggests that expression of PDX-1 increases after pancreatectomy. 3) KGFR was expressed in α-cells of the pancreatic islets implying that KGF contributes to the functional differentiation of the α-cells.B. L-arginine-induced pancreatitis1) Six hours after L-arginine injection, interstitial edema was observed in the pancreas, whereas on day 4 postinjection, there was severe pancreatic necrosis. 2) Neovascularization and ductal-ductular proliferation were also present in the pancreas. 3) Immunohistochemical analysis revealed increased Ki-67 labeling in acinar cells and capillary endothelial cells. 4) Immunoblotting using anti-nestin 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. 5) 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. Less