کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3296684 | 1209872 | 2008 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Hypoxia-Inducible Factor Augments Experimental Colitis Through an MIF-Dependent Inflammatory Signaling Cascade
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کلمات کلیدی
qPCRDSSHIFARNTVHLTNBSvon Hippel–Lindau tumor suppressor proteinHnf - HNFaryl hydrocarbon nuclear translocator - اتمسفر هسته ای آرویل هیدروکربنTrinitrobenzene sulfonic acid - اسید سولفونیک TrinitrobenzeneDextran sulfate sodium - سولفات سدیم دکسترانMIF - شهرMacrophage migration inhibitory factor - عامل مهارکننده مهاجرت ماکروفاژhepatic nuclear factor - عامل هسته ای کبدHypoxia-inducible factor - فاکتور القاء کننده هیپوکسیquantitative reverse-transcription polymerase chain reaction - واکنش زنجیره ای پلیمراز کمی معکوس رونویسی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Hypoxia-Inducible Factor Augments Experimental Colitis Through an MIF-Dependent Inflammatory Signaling Cascade Hypoxia-Inducible Factor Augments Experimental Colitis Through an MIF-Dependent Inflammatory Signaling Cascade](/preview/png/3296684.png)
چکیده انگلیسی
Background & Aims: Colon epithelial cells are critical for barrier function and contain a highly developed immune response. A previous study has shown hypoxia-inducible factor (HIF) as a critical regulator of barrier protection during colon epithelial injury. However, the role of HIF signaling in colon mucosal immunity is not known. Methods: With the use of cre/loxP technology, intestinal-specific disruption of von Hippel-Lindau tumor suppressor protein (Vhl), hypoxia-inducible factor (Hif)-1α, and aryl hydrocarbon nuclear translocator (Arnt) was generated. Colon inflammation was induced using a dextran sulfate sodium (DSS)-induced colitis model, and the mice were analyzed by histologic analysis, Western blot analysis, and quantitative polymerase chain reaction. Results: In mice, colonic epithelium disruption of Vhl resulted in constitutive expression of HIF, which initiated an increase in inflammatory infiltrates and edema in the colon. These effects were ameliorated in mice by disruption of both Vhl and Arnt/Hif1β (which inactivates HIF). In a DSS-induced colitis model, increased HIF expression correlated with more severe clinical symptoms and an increase in histologic damage, while disruption of both Vhl and Arnt in the colon epithelium inhibited these effects. Furthermore, colons with constitutive activation of HIF displayed increased expression of proinflammatory mediators that were synergistically potentiated following DSS administration and reduced by inhibition of the proinflammatory and direct HIF target gene macrophage migration inhibitory factor. Conclusions: The present study shows that a chronic increase in HIF signaling in the colon epithelial cells initiates a hyperinflammatory reaction that may have important implications in developing therapeutic strategies for inflammatory bowel disease.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 134, Issue 7, June 2008, Pages 2036-2048.e3
Journal: Gastroenterology - Volume 134, Issue 7, June 2008, Pages 2036-2048.e3
نویسندگان
Yatrik M. Shah, Shinji Ito, Keiichirou Morimura, Chi Chen, Sun-Hee Yim, Volker H. Haase, Frank J. Gonzalez,