Altered bone morphogenetic protein signalling in the Helicobacter pylori-infected stomach
Altered bone morphogenetic protein signalling in the Helicobacter pylori-infected stomach
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DOI：
10.1002/path.1976
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发表时间：
2006-06-01
影响因子：
7.3
通讯作者：
van den Brink, G. R.
中科院分区：
文献类型：
--
作者：
Bleuming, S. A.;Kodach, L. L.;van den Brink, G. R.
形态发生素调节成人胃肠道上皮细胞的命运决定。作者假设炎性细胞流入固有层可能会干扰胃肠道上皮中形态发生素（形态发生景观）的正常表达梯度。因此，在正常和幽门螺杆菌感染的胃粘膜骨形态发生蛋白（BMP）途径的活性的变化进行了检查。它表明，BNIP受体，激活（磷酸化）形式的细胞内BNIP信号转导蛋白SMAD1，和BMP目标ID2都定位于胃上皮细胞，在正常粘膜上皮更新轴的末端。H.幽门螺杆菌感染与BMP 2表达增加有关，这是由于产生BMP 2的炎性细胞的流入。此外，在正常胃窦中未检测到BMP 4，而在H.幽门感染的胃这种BMP表达细胞的流入与上皮BNIP信号传导的增加有关。有趣的是，观察到BNIP途径的活性向胃单位的前体细胞隔室（峡部）转移。因此，H.幽门螺杆菌感染导致炎性细胞的流入，其干扰在上皮细胞命运调节中具有既定作用的形态发生途径的正常活性梯度。这些数据表明，上皮组织学的形态学变化可能是由于固有层细胞组成的变化继发于形态发生景观的改变。版权所有（c）2006大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
Morphogens regulate epithelial cell fate decisions in the adult gastrointestinal tract. The authors hypothesized that influx of inflammatory cells into the lamina propria may disturb the normal expression gradients of morphogens (morphogenetic landscape) in gastrointestinal epithelia. Changes in the activity of the bone morphogenetic protein (BMP) pathway in normal and Helicobacter pylori-infected gastric mucosa were therefore examined. It is shown that BNIP receptors, the activated (phosphorylated) form of the intracellular BNIP signal transduction protein SMAD1, and BMP target ID2 all localize to gastric epithelial cells that are at the end of the axis of epithelial renewal in normal mucosa. Colonization of human gastric mucosa with H. pylori was associated with an increase in BMP2 expression due to influx of inflammatory cells that produce BMP2. Furthermore, whereas no BMP4 was detected in the normal antrum, focal infiltrates of BMP4-expressing cells were found in the H. pylori-infected stomach. This influx of BMP-expressing cells was associated with an increase in epithelial BNIP signalling. Interestingly, a shift in activity of the BNIP pathway was observed towards the precursor cell compartment (isthmus) of the gastric units. Thus, H. pylori infection results in an influx of inflammatory cells that disturb the normal activity gradient of a morphogenetic pathway with an established role in epithelial cell fate regulation. The data suggest that morphological changes in epithelial histology may result from alterations in the morphogenetic landscape secondary to changes in the cellular composition of the lamina propria. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.