| First Author | Talmasov D | Year | 2015 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 308 |
| Issue | 2 | Pages | G121-38 |
| PubMed ID | 25414097 | Mgi Jnum | J:223878 |
| Mgi Id | MGI:5660570 | Doi | 10.1152/ajpgi.00080.2014 |
| Citation | Talmasov D, et al. (2015) Kruppel-like factor 4 is a radioprotective factor for the intestine following gamma-radiation-induced gut injury in mice. Am J Physiol Gastrointest Liver Physiol 308(2):G121-38 |
| abstractText | Gut radiation-induced injury is a concern during treatment of patients with cancer. Kruppel-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 gamma-irradiation in vitro. We sought to determine whether KLF4 mediates the small intestinal response to gamma-irradiation in vivo. Mice with intestinal epithelium-specific deletion of Klf4 (Klf4(DeltaIS)) and control (Klf4(fl/fl)) mice were irradiated with total-body gamma-radiation. Following irradiation, the Klf4(DeltaIS) 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(DeltaIS) 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(DeltaIS) 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 gamma-irradiation by inhibiting apoptosis in the acute response to irradiation and contributing to crypt regeneration. |
