BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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:Klf5expression 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: Amitava Das; Martin E Fernandez-Zapico; Sheng Cao; Janet Yao; Stefano Fiorucci; Robert P Hebbel; Raul Urrutia; Vijay H Shah Journal: J Biol Chem Date: 2006-10-27 Impact factor: 5.157
Authors: Ainara Ruiz de Sabando; Chao Wang; Yuanjun He; Mónica García-Barros; Julie Kim; Kenneth R Shroyer; Thomas D Bannister; Vincent W Yang; Agnieszka B Bialkowska Journal: Mol Cancer Ther Date: 2015-11-30 Impact factor: 6.261
Authors: Laurianne Van Landeghem; M Agostina Santoro; Amanda T Mah; Adrienne E Krebs; Jeffrey J Dehmer; Kirk K McNaughton; Michael A Helmrath; Scott T Magness; P Kay Lund Journal: FASEB J Date: 2015-04-02 Impact factor: 5.191
Authors: Mandayam O Nandan; Amr M Ghaleb; Yang Liu; Agnieszka B Bialkowska; Beth B McConnell; Kenneth R Shroyer; Sylvie Robine; Vincent W Yang Journal: Dev Biol Date: 2014-01-15 Impact factor: 3.582
Authors: Emre Turer; William McAlpine; Kuan-Wen Wang; Tianshi Lu; Xiaohong Li; Miao Tang; Xiaoming Zhan; Tao Wang; Xiaowei Zhan; Chun-Hui Bu; Anne R Murray; Bruce Beutler Journal: Proc Natl Acad Sci U S A Date: 2017-01-30 Impact factor: 11.205
Authors: Sanjay Chahar; Vishal Gandhi; Shiyan Yu; Kinjal Desai; Richard Cowper-Sal-lari; Yona Kim; Ansu O Perekatt; Namit Kumar; Joshua K Thackray; Anthony Musolf; Nikhil Kumar; A Hoffman; Douglas Londono; Berta N Vazquez; Lourdes Serrano; Hyunjin Shin; Mathieu Lupien; Nan Gao; Michael P Verzi Journal: Mol Cell Biol Date: 2014-06-30 Impact factor: 4.272