title: Krüppel-like factor 5 protects against dextran sulfate sodium-induced colonic injury in mice by promoting epithelial repair.
abstract: OBJECTIVE
  Krüppel-like factor 5 (KLF5) is a transcription factor that promotes proliferation, is highly expressed in dividing crypt cells of the gastrointestinal epithelium, and is induced by various stress stimuli. We sought to determine the role of KLF5 in colonic inflammation and recovery by studying mice with dextran sulfate sodium (DSS)-induced colitis.
  
  
  METHODS
  Wild-type (WT) and Klf5(+/-) mice were given DSS in the drinking water to induce colitis. For recovery experiments, mice were given normal drinking water for 5 days after DSS administration. The extent of colitis was determined using established clinical and histological scoring systems. Immunohistochemical and immunoblotting analyses were used to examine proliferation, migration, and expression of the epidermal growth factor receptor.
  
  
  RESULTS
  Klf5 expression was increased in colonic tissues of WT mice given DSS; induction of Klf5 was downstream of mitogen-activated protein kinase signaling. In DSS-induced colitis, Klf5(+/-) mice exhibited greater sensitivity to DSS than WT mice, with significantly higher clinical and histological colitis scores. In recovery experiments, Klf5(+/-) mice showed poor recovery, with continued weight loss and higher mortality than WT mice. Klf5(+/-) mice from the recovery period had reduced epithelial proliferation and cell migration at sites of ulceration compared to WT mice; these reductions correlated with reduced expression of epidermal growth factor receptor.
  
  
  CONCLUSIONS
  Epithelial repair is an important aspect of recovery from DSS-induced colitis. The transcription factor KLF5 regulates mucosal healing through its effects on epithelial proliferation and migration.
authors.affiliation: Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA. beth.mcconnell@emory.edu
authors.forename: Beth B
authors.initials: BB
authors.lastname: McConnell
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Kim
authors.forename: Agnieszka B
authors.initials: AB
authors.lastname: Bialkowska
authors.forename: Ke
authors.initials: K
authors.lastname: Yu
authors.forename: Shanthi V
authors.initials: SV
authors.lastname: Sitaraman
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Yang
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis; D012038:Regeneration
chemical_list: C118391:Klf5 protein, mouse; D051741:Kruppel-Like Transcription Factors; D016264:Dextran Sulfate; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases