کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3294555 1209842 2012 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Deficiency of Claudin-18 Causes Paracellular H+ Leakage, Up-regulation of Interleukin-1β, and Atrophic Gastritis in Mice
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Deficiency of Claudin-18 Causes Paracellular H+ Leakage, Up-regulation of Interleukin-1β, and Atrophic Gastritis in Mice
چکیده انگلیسی

Background & AimsAlthough defects in tight junction (TJ) epithelial paracellular barrier function are believed to be a primary cause of inflammation, the mechanisms responsible remain largely unknown.MethodsWe generated knockout mice of stomach-type claudin-18, a major component of TJs in the stomach.ResultsCldn18−/− mice were afflicted with atrophic gastritis that started on postnatal day 3. This coincided with a decrease in intragastric pH due to H+ secretion from parietal cells and concomitant up-regulation of the cytokines, interleukin-1β, cyclooxygenase-2, and KC, resulting in spasmolytic polypeptide-expressing metaplasia (SPEM). Oral administration of hydrochloric acid on postnatal day 1 induced the expression of these cytokines in Cldn18−/− infant stomach, but not in Cldn18+/+ mice. A paracellular H+ leak in Cldn18−/− stomach was detected by electrophysiology and H+ titration, and freeze-fracture electron microscopy showed structural defects in the TJs, in which the tightly packed claudin-18 (stomach-type)-based TJ strands were lost, leaving a loose meshwork of strands consisting of other claudin species.ConclusionsThese findings provide evidence that claudin-18 normally forms a paracellular barrier against H+ in the stomach and that its deficiency causes paracellular H+ leak, a persistent up-regulation of proinflammatory cytokines, chronic recruitment of neutrophils, and the subsequent development of SPEM in atrophic gastritis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 142, Issue 2, February 2012, Pages 292–304
نویسندگان
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