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  • Title: Raf protects against colitis by promoting mouse colon epithelial cell survival through NF-kappaB.
    Author: Edelblum KL, Washington MK, Koyama T, Robine S, Baccarini M, Polk DB.
    Journal: Gastroenterology; 2008 Aug; 135(2):539-51. PubMed ID: 18598699.
    Abstract:
    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-kappaB 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-kappaB 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.
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