Raf Protects Against Colitis by Promoting Mouse Colon Epithelial Cell Survival Through NF-κB

Karen L. Edelblum, M. Kay Washington, Tatsuki Koyama, Sylvie Robine, Manuela Baccarini, D. Brent Polk

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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-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.

Original languageEnglish (US)
Pages (from-to)539-551.e3
JournalGastroenterology
Volume135
Issue number2
DOIs
StatePublished - Aug 2008

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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