Distribution of the H+/peptide transporter PepT1 in human intestine:: up-regulated expression in the colonic mucosa of patients with short-bowel syndrome

Distribution of the H+/peptide transporter PepT1 in human intestine:: up-regulated expression in the colonic mucosa of patients with short-bowel syndrome
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DOI:
10.1093/ajcn/75.5.922
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发表时间:
2002-05-01
影响因子:
7.1
通讯作者:
Leader, LM
Leader, LM
中科院分区:
医学1区
文献类型:
--
作者:
Ziegler, TR;Fernández-Estívariz, C;Leader, LM

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背景:动物模型中大规模肠切除后肠道适应的特点是肠道粘膜生长和营养转运蛋白表达增加。关于患有短肠综合征 (SBS) 的人类中这些指标的数据很少。目的:目的是比较患有或不患有 SBS 的成人的小肠和结肠粘膜生长以及肽转运蛋白 PepT I 的表达。设计:粘膜活检标本取自 33 名具有完整肠道的对照受试者和 13 名依赖肠外营养的 SBS 患者的小肠和结肠,因为 慢性吸收不良。测量肠粘膜隐窝深度、绒毛高度和绒毛宽度,并通过Northern印迹、原位杂交和免疫组化检测PepT1表达。结果:2组间小肠和结肠粘膜生长指标无显着差异。 PepT1 在十二指肠、空肠和回肠绒毛上皮细胞的顶端区域高表达;两组远端小肠的吸收性结肠细胞含量较低,且无显着差异。然而,SBS 患者结肠中 PepT1 mRNA 的丰度是对照受试者的 5 倍以上 (P < 0.01)。结论:SBS 患者的肠道适应似乎并不涉及肠粘膜隐窝深度或绒毛大小的增加。 PepT I 在人类小肠刷状缘大量存在;结肠中的表达表明大肠具有腔内二肽和三肽转运机制。 SBS 中结肠 PepT1 的上调可能会适应性地改善吸收不良的二肽和三肽的累积,而与粘膜表面积的变化无关。
Background: Intestinal adaptation after massive bowel resection in animal models is characterized by increased gut-mucosal growth and expression of nutrient transporters. Few data about these indexes exist in humans with short-bowel syndrome (SBS).Objective: The objective was to compare small-bowel and colonic mucosal growth and expression of the peptide transporter PepT I in adults with or without SBS.Design: Mucosal biopsy specimens were obtained from the small bowel and colon of 33 control subjects with intact intestine and from 13 SBS patients dependent on parenteral nutrition because of chronic malabsorption. Gut-mucosal crypt depth, villus height, and villus width were measured, and expression of PepT1 was determined by Northern blotting, in situ hybridization, and immunohistochemistry.Results: The indexes of small-bowel and colonic mucosal growth were not significantly different between the 2 groups. PepT1 expression was high in the apical region of duodenal, jejunal, and ileal villus epithelial cells; low in absorptive colonocytes and not significantly different in the distal small intestine of the 2 groups. However, the abundance of PepT1 mRNA in the colon of SBS patients was more than 5-fold that in control subjects (P < 0.01).Conclusions: Gut adaptation in SBS patients does not appear to involve an increase in gut-mucosal crypt depth or villus size. PepT I is abundant along the small-bowel brush border in humans; expression in the colon indicates that the large intestine has a mechanism for luminal di- and tripeptide transport. Up-regulation of colonic PepT1 in SBS may adaptively improve accrual of malabsorbed di- and tripeptides, independent of changes in the mucosal surface area.