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• W3140331381 abstract "specific Klf4 deletion (Klf4ΔIS) and control mice with floxed Klf4 gene (Klf4fl/fl) were treated or not with 3% dextran sodium sulfate (DSS) for 7 days and the extent of DSS-induced colonic inflammation was then assessed. To demonstrate the therapeutic efficacy of Klf4siRNA use for experimental murine colitis, WT mice were given or not nanoparticles (NP) loaded with scrambled or Klf4-siRNA and concomitantly treated or not with DSS. RESULTS: Compared to DSS-treated Klf4fl/fl mice, DSS-treated Klf4ΔIS mice had significantly lower clinical scores. Histological analysis showed that DSS-treated Klf4 ΔIS mice had much less epithelial cell loss in the colon compared to DSS-treated Klf4fl/fl mice. DSS treatment of Klf4fl/fl mice induced Klf4 expression in the crypt zone of the colonic epithelium where Klf4 is normally absent. In contrast, DSS-treated Klf4 ΔIS mice had increased proliferation relative to DSS-treated control. Western blot analysis showed that Klf4 level was increased in DSS-treated Klf4fl/fl mice in a time-dependent manner, peaking at day 3 of treatment. NF-κB activation was reduced in the colon of DSS-treated Klf4 ΔIS mice as indicated by elevated IκB level and this was accompanied by a significantly lower inflammatory profile compared to DSS-treated Klf4fl/fl mice. Compared toWT mice given DSS and NP/scrambledsiRNA, WT mice given DSS and NP/Klf4-siRNA had significantly reduced both weight loss and overall clinical score. Also, Klf4 expression in the crypt zone was inhibited accompanied by an increase in the proliferative response of the epithelium. CONCLUSIONS: Inhibition of Klf4 expression in mice colon attenuates the inflammatory response and increases the proliferative/regenerative response following DSS treatment. Klf4 is therefore an important factor that mediates DSS-induced colonic inflammation and could be involved in the pathogenesis and/or propagation of IBD. Klf4 may represent a novel therapeutic target in IBD." @default.
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• W3140331381 date "2013-01-01" @default.
• W3140331381 modified "2023-09-27" @default.
• W3140331381 title "Tu1626 A Probiotic-Derived Polyphosphate Improves Chronic Inflammation and Fibrosis via Caveolin-Dependent Endocytosis" @default.
• W3140331381 hasPublicationYear "2013" @default.
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