JCI table of contents: January 2, 2007

ACCOMPANYING COMMENTARY

TITLE: A dominant role for glucose in beta-cell compensation of insulin resistance

AUTHOR CONTACT:

Gordon C. Weir
Joslin Diabetes Center, Boston, Massachusetts, USA.
Phone: (617) 732-2581; Fax: (617) 732-2650; E-mail: .
View the PDF of this article at: https://www.the-jci.org/article.php?id=30862

GASTROENTEROLOGY

Cell relocation fixes damage to the gut lining

The cells lining the intestine (epithelial cells) function as a barrier that keeps the contents of our intestines separate from our body tissues. Damage to the epithelial cell layer allows the contents of our intestines, including our gut bacteria, access to our tissues and bloodstream; large numbers of bacteria in the bloodstream can result in the life-threatening condition septicemia. Therefore, rapid repair of the epithelial cell layer after damage is essential. In a study appearing in the January issue of the Journal of Clinical Investigation, researchers from Washington University School of Medicine, St. Louis, have identified what they believe is a new mechanism by which the epithelial cell layer of the mouse intestine is repaired after damage.

Thaddeus Stappenbeck and colleagues showed that repair of the epithelial cell layer of the mouse rectum by proliferation of colonic epithelial progenitors (ColEPs) required the presence of two proteins -- Myd88 and Ptgs2. Myd88 is a signaling protein that was shown to be upstream of the requirement for Ptgs2. Surprisingly, Myd88 signaling did not induce increased expression of Ptgs2 and instead caused the relocation of Ptgs2-expressing stromal cells in the intestinal tissues to sites in the epithelial cell layer rich in ColEPs. Further studies will be required to determine whether the Ptgs2-expressing stromal cells directly or indirectly induce ColEP proliferation and whether similar cellular relocation mechanisms control progenitor cell proliferation in other tissues.

In an accompanying commentary, Seth Rakoff-Nahoum and Ruslan Medzhitov from Yale University School of Medicine, propose a model whereby damage to the epithelial cell layer of the intestine allows immune cells in the intestinal tissues to sense gut bacteria and initiate Myd88 signaling, which results in them instructing nearby Ptgs2-expressing stromal cells to relocate to sites in the epithelial cell layer rich in ColEPs.