| First Author | Edelblum KL | Year | 2008 |
| Journal | Gastroenterology | Volume | 135 |
| Issue | 2 | Pages | 539-51 |
| PubMed ID | 18598699 | Mgi Jnum | J:141890 |
| Mgi Id | MGI:3819996 | Doi | 10.1053/j.gastro.2008.04.025 |
| Citation | Edelblum KL, et al. (2008) Raf protects against colitis by promoting mouse colon epithelial cell survival through NF-kappaB. Gastroenterology 135(2):539-51 |
| abstractText | 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. |
