title: Krüppel-like factor 4 is a radioprotective factor for the intestine following γ-radiation-induced gut injury in mice.
abstract: Gut radiation-induced injury is a concern during treatment of patients with cancer. Krüppel-like factor 4 (KLF4) is expressed in differentiated villous epithelial cells of the small intestine. We previously showed that KLF4 protects cells from apoptosis following γ-irradiation in vitro. We sought to determine whether KLF4 mediates the small intestinal response to γ-irradiation in vivo. Mice with intestinal epithelium-specific deletion of Klf4 (Klf4(ΔIS)) and control (Klf4(fl/fl)) mice were irradiated with total-body γ-radiation. Following irradiation, the Klf4(ΔIS) mice had significantly increased mortality compared with irradiated Klf4(fl/fl) mice. Immunohistochemistry and immunofluorescence staining were used to assess the morphological changes, levels of proliferation, and apoptosis in the intestinal epithelium. At 96 h following irradiation, there was a regenerative response manifested by an expansion of the proliferative zone in both mouse groups, with the control mice having a higher proliferative activity than the Klf4(ΔIS) group. In addition, there was a significant increase in the number of Klf4/Ki67-copositive cells in the irradiated control mice compared with unirradiated mice. Also, the irradiated Klf4(ΔIS) mice had a significantly higher number of crypt cells positive for apoptosis, p53, and p21 compared with irradiated Klf4(fl/fl) mice. Taken together, our data suggest that Klf4 may function as a radioprotective factor against gastrointestinal syndrome in mice following γ-irradiation by inhibiting apoptosis in the acute response to irradiation and contributing to crypt regeneration.
authors.affiliation: Department of Medicine, Stony Brook University, Stony Brook, New York; and.
authors.forename: Daniel
authors.initials: D
authors.lastname: Talmasov
authors.affiliation: Department of Gastroenterology, the Affiliated Hospital of Ningbo University School of Medicine, Ningbo, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Xinjun
authors.affiliation: Department of Medicine, Stony Brook University, Stony Brook, New York; and.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Medicine, Stony Brook University, Stony Brook, New York; and.
authors.forename: Mandayam O
authors.initials: MO
authors.lastname: Nandan
authors.affiliation: Department of Medicine, Stony Brook University, Stony Brook, New York; and.
authors.forename: Agnieszka B
authors.initials: AB
authors.lastname: Bialkowska
authors.affiliation: Department of Medicine, Stony Brook University, Stony Brook, New York; and.
authors.forename: Enas
authors.initials: E
authors.lastname: Elkarim
authors.affiliation: Department of Medicine, Stony Brook University, Stony Brook, New York; and.
authors.forename: Jes
authors.initials: J
authors.lastname: Kuruvilla
authors.affiliation: Department of Medicine, Stony Brook University, Stony Brook, New York; and.
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Yang
authors.affiliation: Department of Medicine, Stony Brook University, Stony Brook, New York; and amr.ghaleb@stonybrookmedicine.edu.
authors.forename: Amr M
authors.initials: AM
authors.lastname: Ghaleb
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000528:radiation effects; D004195:Disease Models, Animal; D005720:Gamma Rays; D007413:Intestinal Mucosa / Q000293:injuries* / Q000378:metabolism*; D007422:Intestines / Q000528:radiation effects; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D014157:Transcription Factors / Q000235:genetics
chemical_list: C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors
keywords: Krüppel-like factor 4; apoptosis; intestinal epithelium; proliferation; γ-irradiation