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

• Published in: PloS one Vol. 10; no. 8; p. e0134212
• Main Authors: Qu, Dongfeng, Weygant, Nathaniel, May, Randal, Chandrakesan, Parthasarathy, Madhoun, Mohammad, Ali, Naushad, Sureban, Sripathi M, An, Guangyu, Schlosser, Michael J, Houchen, Courtney W
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.08.2015; Public Library of Science (PLoS)
• Subjects: Ablation; Adenomatous polyposis coli; Analysis; Animal models; Animals; Apoptosis - drug effects; Apoptosis - genetics; Cell Proliferation - drug effects; Cell Proliferation - genetics; Chemokines; Colitis; Colitis - chemically induced; Colitis - enzymology; Colitis - genetics; Colitis - pathology; Colon; Colon - drug effects; Colon - metabolism; Colon - pathology; Colon cancer; Colorectal cancer; Cytokines; Dextran; Dextran sulfate; Dextran Sulfate - adverse effects; Dextrans; Doublecortin protein; Doublecortin-Like Kinases; Drinking water; Epithelial cells; Epithelium; Experiments; Feces; Gene Deletion; Gene expression; Health sciences; Immunoblotting; Inflammation; Inflammatory bowel disease; Inflammatory response; Integrity; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Intestine; Male; Medicine; Mice; Molecular weight; Pathogenesis; Permeability; Protein Serine-Threonine Kinases - deficiency; Protein Serine-Threonine Kinases - genetics; Rodents; Sodium; Stem cell transplantation; Stem cells; Stem Cells - drug effects; Sulfates; Veterans; Wnt protein; β-Catenin; Beijing China; United States > US; Oklahoma; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0134212

Doublecortin-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.