The peptide transporter PEPT1 is expressed in distal colon in rodents and humans and contributes to water absorption.
The peptide transporter PEPT1 is expressed in distal colon in rodents and humans and contributes to water absorption.
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DOI：
10.1152/ajpgi.00491.2012
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发表时间：
2013-07
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影响因子：
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通讯作者：
Tilo Wuensch;S. Schulz;Sina S Ullrich;N. Lill;T. Stelzl;I. Rubio-Aliaga;G. Loh;M. Chamaillard;D. Haller;H. Daniel
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作者：
Tilo Wuensch;S. Schulz;Sina S Ullrich;N. Lill;T. Stelzl;I. Rubio-Aliaga;G. Loh;M. Chamaillard;D. Haller;H. Daniel
多肽转运体PEPT1表达于肠上皮细胞刷状缘膜，介导小肠对腔蛋白消化的双肽和三肽的摄取。PEPT1被认为在正常的结肠粘膜中不表达，但在炎症性状态下可能会被检测到，如克罗恩病或溃疡性结肠炎。我们通过系统分析小鼠、大鼠和人类健康结肠组织中PEPT1的mRNA和蛋白水平，重新评估了PEPT1的表达。对不同品系小鼠(C57BL/6N、129/Sv、BALB/c)的免疫荧光分析表明，PEPT1存在于结肠远端，而不存在于近端。大鼠和人的肠道中PEPT1的分布与小鼠相似。然而，在人乙状结肠的定位显示，免疫反应存在于低水平的顶膜，但在不同的细胞内间隔大量染色。用[≈⁴C]Gly-Sar对小鼠结肠组织中PEPT1的功能活性进行了评估，发现远端结肠组织中PEPT1的功能活性是近端结肠组织的5.7倍。在PEPT1-/-小鼠的肠道组织中，没有检测到[⁴C]Gly-Sar转运，但粪便样本显示的水分含量显著高于野生型小鼠，这表明PEPT1有助于结肠水的吸收。总之，我们的研究明确地证明了PEPT1蛋白在小鼠、大鼠和人类健康的远端结肠上皮中的存在，并证明了该蛋白具有功能，并有助于小鼠的电解质和水的处理。
The peptide transporter PEPT1, expressed in the brush border membrane of enterocytes, mediates the uptake of di- and tripeptides from luminal protein digestion in the small intestine. PEPT1 was proposed not to be expressed in normal colonic mucosa but may become detectable in inflammatory states such as Crohn's disease or ulcerative colitis. We reassessed colonic expression of PEPT1 by performing a systematic analysis of PEPT1 mRNA and protein levels in healthy colonic tissues in mice, rats, and humans. Immunofluorescence analysis of different mouse strains (C57BL/6N, 129/Sv, BALB/c) demonstrated the presence of PEPT1 in the distal part of the colon but not in proximal colon. Rat and human intestines display a similar distribution of PEPT1 as found in mice. However, localization in human sigmoid colon revealed immunoreactivity present at low levels in apical membranes but substantial staining in distinct intracellular compartments. Functional activity of PEPT1 in colonic tissues from mice was assessed in everted sac preparations using [¹⁴C]Gly-Sar and found to be 5.7-fold higher in distal compared with proximal colon. In intestinal tissues from Pept1-/- mice, no [¹⁴C]Gly-Sar transport was detectable but feces samples revealed significantly higher water content than in wild-type mice, suggesting that PEPT1 contributes to colonic water absorption. In conclusion, our studies unequivocally demonstrate the presence of PEPT1 protein in healthy distal colonic epithelium in mice, rats, and humans and proved that the protein is functional and contributes to electrolyte and water handling in mice.