Bacterial colonization leads to the colonic secretion of RELMβ/FIZZ2, a novel goblet cell-specific protein
Bacterial colonization leads to the colonic secretion of RELMβ/FIZZ2, a novel goblet cell-specific protein
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DOI：
10.1016/j.gastro.2003.07.009
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发表时间：
2003-11-01
期刊：
影响因子：
29.4
通讯作者：
Wu, GD
中科院分区：
文献类型：
--
作者：
He, WM;Wang, ML;Wu, GD
背景与目的：杯状细胞是在小肠和大肠中发现的高度极化的外分泌细胞，由于顶端分泌颗粒的积累而具有特征性的形态。这些颗粒含有在细胞保护、屏障功能和增殖中起重要生理作用的蛋白质。已经确定了数量有限的肠杯细胞特异性蛋白质。在这项研究中，我们研究了一种新的结肠特异性基因RELMbeta的表达和调控。方法：测定LS174T、Caco-2和HT-29细胞系在白细胞介素13和脂多糖刺激下RUMP信使RNA表达的变化。采用定量逆转录聚合酶链反应、免疫印迹和免疫组织化学检测RELMbeta在BALB/c和c . b17中的表达。将SCID小鼠置于常规、无菌和非生物环境中。结果：RELMbeta的信使RNA仅限于未分化的增殖结肠上皮。免疫组织化学显示该蛋白主要在位于结肠和盲肠远端一半的杯状细胞中表达，在近端结肠中可检测到较低水平。在小鼠和人类的粪便中可以检测到高水平的RELMbeta，在非还原条件下，它以同型二聚体的形式存在。有趣的是，在无菌小鼠中，RELMbeta的分泌显著减少。此外，将无菌小鼠引入常规环境可在48小时内增强RELMbeta的表达和强劲分泌。结论：这些研究定义了一种新的杯状细胞特异性蛋白，并首次提供了结肠特异性基因表达可以通过正常肠道细菌定植来调节的证据。
Background & Aims: Goblet cells are highly polarized exocrine cells found throughout the small and large intestine that have a characteristic morphology due to the accumulation of apical secretory granules. These granules contain proteins that play important physio-logic roles in cellular protection, barrier function, and proliferation. A limited number of intestinal goblet cell-specific proteins have been identified. In this study, we investigate the expression and regulation of RELMbeta, a novel colon-specific gene. Methods: The regulation of RUMP messenger RNA expression was determined in LS174T, Caco-2, and HT-29 cell lines in response to stimulation with interleukin 13 and lipopolysaccharide. Quantitative reverse-transcription polymerase chain reaction, immunoblots, and immunohistochemistry were used to examine the expression of RELMbeta in BALB/c and C.B17.SCID mice housed in conventional, germfree, and gnotobiotic environments. Results: Messenger RNA for RELMbeta is restricted to the undifferentiated, proliferating colonic epithelium. Immunohistochemistry shows that this protein is expressed in goblet cells located primarily in the distal half of the colon and cecum with lower levels detectable in the proximal colon. High levels of RELMbeta can be detected in the stool of mice and humans, where it exists as a homodimer under nonreducing conditions. Interestingly, the secretion of RELMbeta is dramatically reduced in germ-free mice. Furthermore, introduction of germ-free mice into a conventional environment results in enhanced expression and robust secretion of RELMbeta within 48 hours. Conclusions: These studies define a new goblet cell-specific protein and provide the first evidence that colon-specific gene expression can be regulated by colonization with normal enteric bacteria.