Altered intestinal epithelial homeostasis in mice with intestine-specific deletion of the Krüppel-like factor 4 gene

Abstract

The zinc finger transcription factor, Krüppel-like factor 4 (KLF4), is expressed in the post-mitotic, differentiated epithelial cells lining the intestinal tract and exhibits a tumor suppressive effect on intestinal tumorigenesis. Here we report a role for KLF4 in maintaining homeostasis of intestinal epithelial cells. Mice with conditional ablation of the Klf4 gene from the intestinal epithelium were viable. However, both the rates of proliferation and migration of epithelial cells were increased in the small intestine of mutant mice. In addition, the brush-border alkaline phosphatase was reduced as was expression of ephrine-B1 in the small intestine, resulting in mispositioning of Paneth cells. In the colon of mutant mice, there was a reduction of the differentiation marker, carbonic anhydrase-1, and failure of differentiation of goblet cells. Mechanistically, deletion of Klf4 from the intestine resulted in a general activation of genes in the Wnt pathway and a global reduction in expression of genes encoding regulators of differentiation. Taken together, these data provide new insights into the function of KLF4 in regulating postnatal proliferation, migration, differentiation, and positioning of intestinal epithelial cells and demonstrate an essential role for KLF4 in maintaining normal intestinal epithelial homeostasis in vivo.

Escherichia coli lipopolysaccharide affects intestinal mucin secretion in weaned pigs

“…Goblet cells differentiate from endoderm stem cells in that they are found deeply in the crypts, and when mature they migrate to the villous surface (Dunsford et al ., 1991). Therefore, it can be suggested that increase in neutral mucins during post-weaning is related to variation in villi and crypt depth, affecting goblet cell differentiation and normal maturation (Ghaleb et al ., 2011).…”

Regulation of the Potential Marker for Intestinal Cells, Bmi1, by β-Catenin and the Zinc Finger Protein KLF4

“…KLF4 is one of the four factors that induce pluripotent stem cells; thus playing a crucial role in stem cell regulation (6,7). In a normal intestine, KLF4 inhibits proliferation of crypt progenitor cells and regulates the differentiation of goblet and Paneth cells (8,9).…”

Role of Krüppel-like factor 5 in the maintenance of the stem cell niche in the intestinal crypt

“…KLF4, also called gut-enriched Krüppel-like factor or GKLF, was initially found to be expressed in the intestine [35] and subsequently in epithelial cells of the skin, therefore also named epithelial zinc finger (EZF) [36] . In the intestine, KLF4 is primarily expressed in the terminally differentiated cells of the intestinal epithelium, where it maintains a quiescent state by negatively regulating the cell cycle [35,37] . Intestine-specific deletion of Klf4 in mice results in increased proliferation and altered differentiation [37] .…”

“…In the intestine, KLF4 is primarily expressed in the terminally differentiated cells of the intestinal epithelium, where it maintains a quiescent state by negatively regulating the cell cycle [35,37] . Intestine-specific deletion of Klf4 in mice results in increased proliferation and altered differentiation [37] . KLF4 expression is also activated by agents causing DNA damage such as ionizing irradiation [33,38,39] and a recent study indicates that KLF4 is a radio-protective factor for the intestine following ionizing radiation-induced gut injury [34] .…”