Research of pancreatic regeneration by fibroblast growth factor -7 and -10

成纤维细胞生长因子-7和-10对胰腺再生的研究

基本信息

批准号：
15590696
负责人：
ISHIWATA Toshiyuki
金额：
$ 1.28万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590696/
关键词：
fibroblast growth factor FGF-7 FGF-10 pancreatic regeneration KGFR nestin pancreatitis 線維芽細胞増殖因子膵再生 KGFR

项目摘要

Keratinocyte growth factor receptor(KGFR), also known as fibroblast growth factor receptor(FGFR) 2IIIb, is a member of the FGFR family. KGFR is specifically localized in epithelial cells and cell growth or differentiation are induced by FGF-7 or FGF-10. Recently, FGF-10 is reported to participate in the development of fetal pancreas. In normal pancreas, KGFR was strongly localized in alpha cells of islets. This finding suggests that KGFR plays an important role of maintenance of islet cell functions. FGF-7 and FGF-10 were highly expressed in the regenerative process of rat arginine-induced acute pancreatitis and KGFR was detected in regenerative acinar cells. Chronic pancreatitis model using dibutyltin dichloride(DBTC) showed KGFR localization in large number of pancreatic ductal cells and regenerative acinar cells. These evidences may indicate that FGF-7 or FGF-10 contribute to the growth or differentiation of ductal and acinar cells, through KGFR. Nestin is an intermediate filament protein expressed on neuroepithelial stem cells. Nestin-expressing cells were detected in pancreatic islet cells and proposed as a marker for putative islet stem cells. In arginine-induced acute pancreatitis, nestin was strongly expressed in islet cells, proliferating endothelial cells and the stellate cell-myofibroblasts surrounding the ductal-ductular structures. Nestin was localized in mesenchymal cells in fibrotic area of DBTC-induced chronic pancreatitis. These findings may indicate that nestin contribute to the angiogenesis and regeneration of epithelial components in pancreatitis. KGFR-positive and/or nestin-positive cells in pancreatitis may be the progenitor cells of pancreas.

角质形成细胞生长因子受体（KGFR），也称为成纤维细胞生长因子受体（FGFR）2IIIB，是FGFR家族的成员。 KGFR专门定位在上皮细胞中，FGF-7或FGF-10诱导细胞生长或分化。最近，据报道，FGF-10参与胎儿胰腺的发展。在正常的胰腺中，KGFR强烈定位在胰岛的α细胞中。这一发现表明，KGFR在维持胰岛细胞功能的维持中起着重要作用。 FGF-7和FGF-10在大鼠精氨酸诱导的急性胰腺炎的再生过程中高度表达，并在再生腺泡细胞中检测到KGFR。使用二丁基二氯化物（DBTC）的慢性胰腺炎模型显示在大量胰腺导管细胞和再生腺泡细胞中的KGFR定位。这些证据可能表明FGF-7或FGF-10通过KGFR有助于导管和腺泡细胞的生长或分化。 Nestin是一种在神经上皮干细胞上表达的中间细丝蛋白。在胰岛细胞中检测到表达巢蛋白的细胞，并提出作为推定胰岛干细胞的标记。在精氨酸诱导的急性胰腺炎中，Nestin在胰岛细胞中强烈表达，增殖的内皮细胞和导管性导管结构周围的星状细胞毛纤维细胞。 Nestin位于DBTC诱导的慢性胰腺炎的纤维化区域的间充质细胞中。这些发现可能表明Nestin有助于胰腺炎中上皮成分的血管生成和再生。胰腺炎中的KGFR阳性和/或巢蛋白阳性细胞可能是胰腺的祖细胞。