Ablation of Doublecortin-Like Kinase 1 in the Colonic Epithelium Exacerbates Dextran Sulfate Sodium-Induced Colitis.
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.
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America; Department of Veterans Affairs Medical Center, Oklahoma City, OK, 73104, United States of America; Peggy and Charles Stephenson Oklahoma Cancer Center, Oklahoma City, OK, 73104, United States of America.
Dongfeng
D
Qu
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America.
Nathaniel
N
Weygant
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America; Department of Veterans Affairs Medical Center, Oklahoma City, OK, 73104, United States of America.
Randal
R
May
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America; Peggy and Charles Stephenson Oklahoma Cancer Center, Oklahoma City, OK, 73104, United States of America.
Parthasarathy
P
Chandrakesan
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America.
Mohammad
M
Madhoun
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America; Peggy and Charles Stephenson Oklahoma Cancer Center, Oklahoma City, OK, 73104, United States of America.
Naushad
N
Ali
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America; Department of Veterans Affairs Medical Center, Oklahoma City, OK, 73104, United States of America; Peggy and Charles Stephenson Oklahoma Cancer Center, Oklahoma City, OK, 73104, United States of America.
Sripathi M
SM
Sureban
Department of Oncology, Beijing Chaoyang Hospital, Capitol Medicinal University, Beijing, 100020, China.
Guangyu
G
An
COARE Biotechnology, Oklahoma City, OK, 73104, United States of America.
Michael J
MJ
Schlosser
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America; Department of Veterans Affairs Medical Center, Oklahoma City, OK, 73104, United States of America; Peggy and Charles Stephenson Oklahoma Cancer Center, Oklahoma City, OK, 73104, United States of America; COARE Biotechnology, Oklahoma City, OK, 73104, United States of America.
Courtney W
CW
Houchen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000009:adverse effects*; D000089742:Doublecortin-Like Kinases; D017353:Gene Deletion; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics*; D013234:Stem Cells / Q000187:drug effects
D016264:Dextran Sulfate; D000089742:Doublecortin-Like Kinases; C485525:Dclk1 protein, mouse; D017346:Protein Serine-Threonine Kinases