Expression and the role of fibroblast growth factor (FGF)-10 in chronic pancreatitis

急性和慢性胰腺炎的再生过程的特征是腺泡和导管细胞增殖，细胞外基质的合成和沉积。各种生长因子与胰腺炎的炎症过程密切相关。成纤维细胞生长因子（FGF）-10和FGF-7，也称为角质形成细胞生长因子（KGF），是FGF家族的成员，并且显示出高度的结构同源性以及相似的生物学特性。两者均由间充质细胞合成，并通过KGF受体（KGFR）刺激上皮细胞。我们在L-精氨酸诱导的大鼠胰腺炎模型中检查了FGF-10、FGF-7和KGFR在胰腺组织中的定位。FGF-10在正常大鼠胰腺中未检测到，但在L-精氨酸诱导的急性胰腺炎中定位于血管平滑肌细胞。FGF-7表达在正常和L-精氨酸处理的胰腺中胰岛的α细胞中是有限的。然后，我们用兔KGFR多克隆抗体检测，发现KGFR免疫反应性定位于正常胰腺的中央腺泡、胰岛和导管细胞，并强烈定位于胰腺炎组织的再生腺泡和胰岛细胞。在尸检的慢性胰腺炎组织中，KGFR主要分布在再生区的导管、腺泡和胰岛细胞中。这些发现表明FGF-10和FGF-7通过KGFR促进急性和慢性胰腺炎的再生过程。

The regenerative process in acute and chronic pancreatitis is characterized by acinar and ductal cell proliferation with synthesis and deposition of extracellular matrices. Various growth factors are closely related to the inflammatory process of pancreatitis. Fibroblast growth factor (FGF)-10 and FGF-7, also known as keratinocyte growth factor (KGF), are members of the FGF family and show high structural homology as well as similar biological characteristics. Both of them are synthesized by mesenchymal cells and stimulate epithelial cells via KGF receptor (KGFR). We examined the localization of FGF-10, FGF-7 and KGFR in pancreatic tissues in an L-arginine-induced rat pancreatitis model. FGF-10 immunoreactivity was not detected in normal rat pancreas, but it was localized in vascular smooth muscle cells in L-arginine-induced acute pancreatitis. FGF-7 expression was limited in the alpha cells of islets in normal and L-arginine-treated pancreata. We then tested with rabbit polyclonal antibody specific for KGFR, and found the KGFR immunoreactivity was localized in centroacinar, islet and ductal cells in normal pancreata and strongly localized in regenerative acinar and islet cells in the pancreatitic tissues. In human chronic pancreatitic tissues from autopsy cases, KGFR was prominently localized in ductal, acinar and islet cells in regenerative regions. These findings suggest that FGF-10 and FGF-7 contribute to the reaenerative process of acute and chronic pancreatitis via KGFR.