Ablation of Doublecortin-Like Kinase 1 in the Colonic Epithelium Exacerbates Dextran Sulfate Sodium-Induced Colitis

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dc.contributor.authorDongfeng Qu
dc.contributor.authorNathaniel Weygant
dc.contributor.authorRandal May
dc.contributor.authorParthasarathy Chandrakesan
dc.contributor.authorMohammad Madhoun
dc.contributor.authorNaushad Ali
dc.contributor.authorSripathi M. Sureban
dc.contributor.authorGuangyu An
dc.contributor.authorMichael J. Schlosser
dc.contributor.authorCourtney W. Houchen
dc.date.accessioned2017-03-05T22:54:59Z
dc.date.available2017-03-05T22:54:59Z
dc.date.issued2015-08-18
dc.descriptionWe would like to acknowledge Jim Henthorn of the University of Oklahoma Health Sciences Center Flow Cytometry and Imaging Core for his assistance in Bio-Plex data collection and analysis.en_US
dc.descriptionen_US
dc.description.abstractDoublecortin-like kinase 1 (Dclk1), a microtubule-associated kinase, marks the fifth lineage of intestinal epithelial cells called tuft cells that function as tumor stem cells in Apc mutant models of colon cancer. In order to determine the role of Dclk1 in dextran sulfate sodium (DSS) induced colonic inflammation both intestinal epithelial specific Dclk1 deficient (VillinCre;Dclk1f/f) and control (Dclk1f/f) mice were fed 3% DSS in drinking water for 9 days, allowed to recover for 2 days, and killed. The clinical and histological features of DSS-induced colitis were scored and immunohistochemical, gene expression, pro-inflammatory cytokines/chemokines, and immunoblotting analyses were used to examine epithelial barrier integrity, inflammation, and stem and tuft cell features. In DSS-induced colitis, VillinCre;Dclk1f/f mice demonstrated exacerbated injury including higher clinical colitis scores, increased epithelial barrier permeability, higher levels of pro-inflammatory cytokines and chemokines, decreased levels of Lgr5, and dysregulated Wnt/b-Catenin pathway genes. These results suggest that Dclk1 plays an important role in regulating colonic inflammatory response and colonic epithelial integrity.en_US
dc.description.peerreviewYesen_US
dc.description.peerreviewnoteshttp://www.plosone.org/static/editorial#peeren_US
dc.identifier.citationQu D, Weygant N, May R, Chandrakesan P, Madhoun M, Ali N, et al. (2015) Ablation of Doublecortin-Like Kinase 1 in the Colonic Epithelium Exacerbates Dextran Sulfate Sodium-Induced Colitis. PLoS ONE 10(8): e0134212. doi:10.1371/journal.pone.0134212en_US
dc.identifier.doi10.1371/journal.pone.0134212en_US
dc.identifier.urihttp://hdl.handle.net/11244/49264
dc.language.isoen_USen_US
dc.publisherPLos One
dc.relation.ispartofseriesPLoS ONE 10(8): e0134212
dc.relation.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0134212
dc.rightsAttribution 3.0 United States
dc.rights.requestablefalseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/
dc.subjectGastrointestinal tract,Mouse models,Colon,Inflammation,Cytokines,Epithelium,Colitis,Gene expressionen_US
dc.titleAblation of Doublecortin-Like Kinase 1 in the Colonic Epithelium Exacerbates Dextran Sulfate Sodium-Induced Colitisen_US
dc.typeResearch Articleen_US

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