Pancreatic duct glands are distinct ductal compartments that react to chronic injury and mediate Shh-induced metaplasia.
Pancreatic duct glands are distinct ductal compartments that react to chronic injury and mediate Shh-induced metaplasia.
复制标题
DOI：
10.1053/j.gastro.2009.12.005
复制
发表时间：
2010-03
期刊：
影响因子：
29.4
通讯作者：
Thayer SP
中科院分区：
文献类型：
--
作者：
Strobel O;Rosow DE;Rakhlin EY;Lauwers GY;Trainor AG;Alsina J;Fernández-Del Castillo C;Warshaw AL;Thayer SP
胰腺上皮内瘤变（PanIN）是起源和意义不明的胰腺癌前病变。PanIN异常表达Sonic Hedgehog（Shh）和胃肠道粘蛋白，Sonic Hedgehog是胰腺癌的起始因子。大多数PanIN被认为是由导管引起的。我们确定了一种新的导管室，聚集在腺样outpouch（胰管腺，PDG）的主要管道和特点的损伤和化生的作用。在人类和小鼠的正常胰腺和慢性胰腺炎中分析导管系统。通过连续H&E切片和腐蚀铸型的扫描电子显微镜来评估解剖结构。通过免疫组织化学或RT-qPCR评估粘蛋白和发育基因的表达以及增殖。通过体外Shh暴露和体内转基因错误表达研究Shh对导管细胞的影响。三维分析显示，在小鼠和人类胰腺的导管盲端outpouch。这些PDG在形态和分子上与正常导管不同;即使在正常胰腺中，它们也显示PanIN和化生特征，例如Shh和胃粘蛋白的表达。它们表达其他发育基因，例如Pdx-1和Hes-1。在损伤中，Shh与胃粘蛋白一起沿着上调。PDG区室的扩张导致粘液性化生。Shh在体外和体内促进这种转化。PDG是具有独特分子特征的独特腺体样粘液隔室。PDG在损伤后发生Shh介导的胃肠道粘液性化生，具有PanIN样特征。PDG可能提供Shh、粘液性化生和瘤形成之间的联系。
Pancreatic intraepithelial neoplasia (PanIN) are pancreatic cancer precursor lesions of unclear origin and significance. PanIN aberrantly express sonic hedgehog (Shh), an initiator of pancreatic cancer, and gastrointestinal mucins. The majority of PanIN are thought to arise from ducts. We identified a novel ductal compartment that is gathered in gland-like outpouches (pancreatic duct glands, PDG) of major ducts and characterized its role in injury and metaplasia. The ductal system was analyzed in normal pancreata and chronic pancreatitis in humans and mice. Anatomy was assessed by serial H&E sections and scanning electron microscopy of corrosion casts. Expression of mucins and developmental genes and proliferation were assessed by immunohistochemistry or RT-qPCR. Effects of Shh on ductal cells were investigated by exposure to Shh in vitro and transgenic misexpression in vivo. Three-dimensional analysis revealed blind-ending outpouches of ducts in murine and human pancreata. These PDG are morphologically and molecularly distinct from normal ducts; even in normal pancreata they display PanIN and metaplastic features such as expression of Shh and gastric mucins. They express other developmental genes, such as Pdx-1 and Hes-1. In injury, Shh is upregulated along with gastric mucins. Expansion of the PDG compartment results in a mucinous metaplasia. Shh promotes this transformation in vitro and in vivo. PDG are a distinct gland-like mucinous compartment with a distinct molecular signature. In response to injury PDG undergo a Shh-mediated mucinous gastrointestinal metaplasia with PanIN-like features. PDG may provide a link between Shh, mucinous metaplasia and neoplasia.
登录
查看更多内容
影响因子：
4.6
作者：
Esni, F;Ghosh, B;Leach, SD
通讯作者：
Leach, SD
DOI：
10.1073/pnas.0810111105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Jean-Paul, De La O.;Emerson, Lyska L.;Murtaugh, L. Charles
通讯作者：
Murtaugh, L. Charles
影响因子：
29.4
作者：
SESSA, F;BONATO, M;SAMLOFF, IM
通讯作者：
SAMLOFF, IM
影响因子：
7.7
作者：
Sharma, A;Zangen, DH;Bonner-Weir, S
通讯作者：
Bonner-Weir, S
影响因子：
29.4
作者：
Strobel, Oliver;Dor, Yuval;Thayer, Sarah P.
通讯作者：
Thayer, Sarah P.