Dimaline Rod, Varro Andrea
Physiological Laboratory, School of Biomedical Sciences, University of Liverpool, Crown Street, Liverpool L69 3BX, UK.
Exp Physiol. 2007 Jul;92(4):591-601. doi: 10.1113/expphysiol.2006.036483. Epub 2007 Apr 5.
The gastric epithelium is a complex structure formed into tubular branched gastric glands. The glands contain a wide variety of cell types concerned with the secretion of hydrochloric acid, proteases, mucus and a range of signalling molecules. All cell types originate from stem cells in the neck region of the gland, before migrating and differentiating to assume their characteristic positions and functions. Endocrine and local paracrine mediators are of crucial importance for maintaining structural and functional integrity of the epithelium, in the face of a hostile luminal environment. The first such mediator to be recognized, the hormone gastrin, was identified over a century ago and is now established as the major physiological stimulant of gastric acid secretion. Recent studies, including those using mice that overexpress or lack the gastrin gene, suggest a number of previously unrecognized roles for this hormone in the regulation of cellular proliferation, migration and differentiation. This review focuses on the identification of hitherto unsuspected gastrin-regulated genes and discusses the paracrine cascades that contribute to the maintenance of gastric epithelial architecture and secretory function. Helicobacter infection is also considered in cases where it shares targets and signalling mechanisms with gastrin.
胃上皮是一种形成管状分支胃腺的复杂结构。这些腺体包含多种与盐酸、蛋白酶、黏液及一系列信号分子分泌相关的细胞类型。所有细胞类型均起源于腺体颈部区域的干细胞，之后迁移并分化以占据其特征性位置并发挥功能。面对恶劣的管腔环境，内分泌和局部旁分泌介质对于维持上皮的结构和功能完整性至关重要。首个被识别的此类介质——胃泌素，于一个多世纪前被鉴定出来，如今已被确立为胃酸分泌的主要生理刺激物。近期的研究，包括那些使用过表达或缺乏胃泌素基因的小鼠所进行的研究，提示了该激素在细胞增殖、迁移和分化调控中一些此前未被认识到的作用。本综述聚焦于迄今未被怀疑的胃泌素调节基因的鉴定，并讨论有助于维持胃上皮结构和分泌功能的旁分泌级联反应。在幽门螺杆菌感染与胃泌素具有共同靶点和信号机制的情况下，也会对其进行探讨。
