کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3295693 1209859 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The PepT1–NOD2 Signaling Pathway Aggravates Induced Colitis in Mice
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
The PepT1–NOD2 Signaling Pathway Aggravates Induced Colitis in Mice
چکیده انگلیسی

Background & AimsThe human di/tripeptide transporter human intestinal H-coupled oligonucleotide transporter (hPepT1) is abnormally expressed in colons of patients with inflammatory bowel disease, although its exact role in pathogenesis is unclear. We investigated the contribution of PepT1 to intestinal inflammation in mouse models of colitis and the involvement of the nucleotide-binding oligomerization domain 2 (NOD2) signaling pathway in the pathogenic activity of colonic epithelial hPepT1.MethodsTransgenic mice were generated in which hPepT1 expression was regulated by the β-actin or villin promoters; colitis was induced using 2,4,6-trinitrobenzene sulfonic acid (TNBS) or dextran sodium sulfate (DSS) and the inflammatory responses were assessed. The effects of NOD2 deletion in the hPepT1 transgenic mice also was studied to determine the involvement of the PepT1–NOD2 signaling pathway.ResultsTNBS and DSS induced more severe levels of inflammation in β-actin–hPepT1 transgenic mice than wild-type littermates. Intestinal epithelial cell–specific hPepT1 overexpression in villin-hPepT1 transgenic mice increased the severity of inflammation induced by DSS, but not TNBS. Bone marrow transplantation studies showed that hPepT1 expression in intestinal epithelial cells and immune cells has an important role in the proinflammatory response. Antibiotics abolished the effect of hPepT1 overexpression on the inflammatory response in DSS-induced colitis in β-actin–hPepT1 and villin-hPepT1 transgenic mice, indicating that commensal bacteria are required to aggravate intestinal inflammation. Nod2−/−, β-actin–hPepT1 transgenic/Nod2−/−, and villin-hPepT1 transgenic/Nod2−/− littermates had similar levels of susceptibility to DSS-induced colitis, indicating that hPepT1 overexpression increased intestinal inflammation in a NOD2-dependent manner.ConclusionsThe PepT1–NOD2 signaling pathway is involved in aggravation of DSS-induced colitis in mice.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 141, Issue 4, October 2011, Pages 1334–1345
نویسندگان
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