van den Brink G R, Hardwick J C H, Nielsen C, Xu C, ten Kate F J, Glickman J, van Deventer S J H, Roberts D J, Peppelenbosch M P
Department of Experimental Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
Gut. 2002 Nov;51(5):628-33. doi: 10.1136/gut.51.5.628.
Sonic hedgehog (Shh) is an important endodermal morphogenetic signal during the development of the vertebrate gut. It controls gastrointestinal patterning in general, and gastric gland formation in particular. We have previously shown that Shh regulates gastric gland proliferation in the adult but detailed analysis of its expression along the adult gastrointestinal tract has never been undertaken. We therefore studied Shh expression along the normal human and rodent adult gastrointestinal tract as well as in intestinal metaplasia of the stomach, gastric and intestinal metaplasia of the oesophagus, and gastric heterotopia in Meckel's diverticulum.
The studies were performed with in situ hybridisation and by immunohistochemistry using an antibody that recognises the Shh precursor form.
We found that in the normal gastrointestinal tract, high levels of Shh were expressed in the fundic glands of the stomach. Shh expression was also found in fundic gland metaplasia and heterotopia. However, Shh expression was lost in intestinal metaplasia of the stomach.
We found a strong correlation between Shh expression and fundic gland differentiation. Our current study therefore provides evidence that in addition to its role in gastric epithelial development, Shh plays a unique role in gastric epithelial differentiation in adults.
音猬因子(Shh)是脊椎动物肠道发育过程中一种重要的内胚层形态发生信号。它总体上控制胃肠道的模式形成,尤其控制胃腺的形成。我们之前已经表明Shh在成体中调节胃腺增殖,但从未对其在成体胃肠道中的表达进行详细分析。因此,我们研究了Shh在正常人和啮齿动物成体胃肠道中的表达情况,以及在胃的肠化生、食管的胃化生和肠化生以及梅克尔憩室中的胃异位组织中的表达情况。
采用原位杂交和免疫组织化学方法进行研究,使用一种识别Shh前体形式的抗体。
我们发现,在正常胃肠道中,胃底腺表达高水平的Shh。在胃底腺化生和异位组织中也发现了Shh表达。然而,胃的肠化生中Shh表达缺失。
我们发现Shh表达与胃底腺分化之间存在密切相关性。因此,我们目前的研究提供了证据,表明Shh除了在胃上皮发育中发挥作用外,在成体胃上皮分化中也发挥独特作用。