Expression and regulation of proton-coupled oligopeptide transporters in colonic tissue and immune cells of mice.
Expression and regulation of proton-coupled oligopeptide transporters in colonic tissue and immune cells of mice.
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质子偶联寡肽转运蛋白在小鼠结肠组织和免疫细胞中的表达与调控
DOI：
10.1016/j.bcp.2017.12.025
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发表时间：
2018-03
影响因子：
5.8
通讯作者：
Smith DE
中科院分区：
文献类型：
--
作者：
Wang Y;Hu Y;Li P;Weng Y;Kamada N;Jiang H;Smith DE
许多研究表明质子偶联寡肽转运蛋白（POTs）参与炎症性肠病和免疫细胞信号传导的启动和/或进展。考虑到这一点，本研究的目的是描绘POTs在小鼠结肠组织和免疫细胞中的表达，并表征这些转运蛋白在核苷酸结合寡聚化结构域（NOD）信号传导中的潜在作用。使用葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型，我们发现DSS下调结肠组织和免疫细胞中Pht 1基因表达，上调Pht 2基因表达。相反，PEPT 1蛋白在正常和DSS处理小鼠的结肠组织和免疫细胞中不存在。NOD配体胞壁酰二肽（MDP）和L-丙氨酸-γ-D-谷氨酸-内消旋-二氨基庚二酸（tri-DAP）在MDCK-hPHT 219，20 AA细胞中被证明是PHT 2的底物。随后的研究表明，固有层单核细胞的免疫应答可能受到PHT 1和PHT 2的调节，并且PHT 2促进RAW 264.7巨噬细胞的NOD依赖性免疫应答。这些结果阐明了POTs在小鼠结肠节段、细胞和亚型中的表达，以及在化学诱导的结肠炎期间Pht 2表达增加在促进NOD依赖性免疫应答中的作用。研究结果进一步表明，肠道PHT 2可能作为IBD治疗的治疗靶点。PEPT 1在小鼠结肠中不存在。DSS诱导的结肠炎上调了PHT 2的表达，其通过跨溶酶体膜转运MDP和tri-DAP促进NOD依赖性免疫应答。
A number of studies have implicated proton-coupled oligopeptide transporters (POTs) in the initiation and/or progression of inflammatory bowel disease and immune cell signaling. With this in mind, the aim of this study was to delineate the expression of POTs in mouse colonic tissues and immune cells, and characterize the potential role of these transporters in nucleotide-binding oligomerization domain (NOD) signaling. Using a dextran sodium sulfate (DSS)-induced colitis mouse model, we found that DSS down regulated Pht1 gene expression and up regulated Pht2 gene expression in colonic tissue and immune cells. In contrast, PEPT1 protein was absent from the colonic tissue and immune cells of normal and DSS-treated mice. NOD ligands, muramyl dipeptide (MDP) and L-Ala-γ-D-Glu-meso-diaminopimelic acid (tri-DAP), were shown to be substrates of PHT2 in MDCK-hPHT219,20AA cells. Subsequent studies revealed that the immune response of lamina propia mononuclear cells may be regulated by PHT1 and PHT2, and that PHT2 facilitated the NOD-dependent immune response in RAW264.7 macrophages. These results clarified the expression of POTs in mouse colonic segments, cells and subtypes, and the role of increased Pht2 expression during chemically-indiced colitis in facilitating NOD-dependent immune response. The findings further suggest that intestinal PHT2 may serve as a therapeutic target for IBD therapy. PEPT1 was absent from colon of mice. DSS-induced colitis upregutated the expression of PHT2, which facilitated the NOD-dependent immune response by transpoting MDP and tri-DAP across lysosomal membrane.
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影响因子：
29.4
作者：
Dalmasso G;Nguyen HT;Ingersoll SA;Ayyadurai S;Laroui H;Charania MA;Yan Y;Sitaraman SV;Merlin D
通讯作者：
Merlin D
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
3.9
作者：
Jappar, Dilara;Wu, Shu-Pei;Smith, David E.
通讯作者：
Smith, David E.
影响因子：
64.8
作者：
Nakamura, Norihiro;Lill, Jennie R.;Mellman, Ira
通讯作者：
Mellman, Ira
影响因子：
7.3
作者：
Moreira LO;Zamboni DS
通讯作者：
Zamboni DS