کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3299309 1209926 2008 16 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Raf Protects Against Colitis by Promoting Mouse Colon Epithelial Cell Survival Through NF-κB
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Raf Protects Against Colitis by Promoting Mouse Colon Epithelial Cell Survival Through NF-κB
چکیده انگلیسی
Background & Aims: Raf-1 kinase is a key regulator of a number of cellular processes, which promote the maintenance of a healthy colon epithelium. This study addresses the role of Raf in epithelial cell survival in response to dextran sulfate sodium (DSS)-induced injury and inflammation. Methods: Inducible intestinal epithelium-specific Raf knockout mice were generated and subjected to acute colitis followed by a short recovery period. Colon sections were analyzed by in situ oligo ligation or immunostaining for Ki67, phospho-extracellular signal regulated kinase, and nuclear factor-κB p65. Western blot analysis and terminal deoxynucleotidyl transferase nick-end labeling assays were performed on Raf small interfering RNA-transfected young adult mouse colon cells following DSS treatment. Results: We report that Raf protects against epithelial injury and inflammation and promotes recovery from acute DSS-induced colitis by both MAPK/ERK kinase (MEK)-dependent and -independent pathways. Furthermore, we demonstrate that Raf induces novel cell survival responses through activating nuclear factor-κB in a MEK-independent manner. Conclusions: These novel findings indicate a protective role for Raf in colon epithelium following ulcerative damage through inhibiting cell apoptosis and promoting proliferation with important implications for responses such as inflammation-associated carcinogenesis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 135, Issue 2, August 2008, Pages 539-551.e3
نویسندگان
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