IBD Guardian

Researchers have identified a molecule that protects colon cells from injury in a mouse model of inflammatory bowel disease (IBD). The study, published by Beth McConnell et al. in the February issue of Gastroenterology, reports that Klf5 controls genes that mediate recovery from colonic injury.

Klf5 regulates transcription of genes involved in proliferation of epithelial cells in the intestine and colon, and is required for repairing injured tissues. McConnell et al. used a mouse model of colitis to examine the role of Klf5 in healing after colon tissue damage. Mice with a disruption in one copy of the gene that encodes Klf5 (Klf5+/– mice) were given the chemical irritant dextran sulfate sodium (DSS) in their drinking water in order to induce a form of colitis that resembles IBD. In normal mice, Klf5 was upregulated in colon cells after administration of DSS.

Mice with reduced levels of Klf5, however, had increased susceptibility to colitis, indicating that Klf5 protects against injury. Furthermore, the Klf5+/– mice did not recover as rapidly as normal mice when DSS was removed from their water. McConnell et al. provide the first evidence that Klf5 is required not only for proliferation of the colonic epithelial cells that mediate repair, but for their migration in the colonic mucosa. The authors identify components of the Klf5 signaling pathway, including epidermal growth factor.

Cells that are proliferating (green) or migrating into ulcerated areas (red) of colons from normal (WT) and Klf5+/– mice. White arrows indicate areas of migration. Many cells in normal mice migrate vertically, within the crypts and across the luminal surface, but cells in Klf5+/– mice migrate less.

The colonic and intestinal epithelium is a barrier against toxic and immunogenic substances. When this barrier is disrupted, the integrity of the surface epithelium is quickly reestablished, even following severe damage. In patients with disorders such as IBD, this barrier is repeatedly disrupted, allowing for increased exposure to infectious agents and toxins that prolong inflammation. Rapid repair of this barrier is required to reduce inflammation and heal lesions in patients with IBD.

McConnell et al. find that Klf5 is required for regeneration of this barrier following damage by regulating proliferation and migration of the epithelial cells. Because efficient epithelial repair is required for recovery from colonic injury, it should be a goal for treatment of patients with IBD.

More Information on IBD:

Read the article online:
McConnell BB, Kim SS, Bialkowska AB, et al. Krüppel-like factor 5 protects against dextran sulfate sodium-induced colonic injury in mice by promoting epithelial repair. Gastroenterology 2011;140:540–549.e2.

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About Kristine Novak, PhD, Science Editor

Dr. Kristine Novak is the science editor for Gastroenterology and Clinical Gastroenterology and Hepatology, both published by the American Gastroenterological Association. She has worked as an editor at biomedical research journals and as a science writer for more than 12 years, covering advances in gastroenterology, hepatology, cancer, immunology, biotechnology, molecular genetics, and clinical trials. She has a PhD in cell biology and an interest in all areas of medical research.
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