The U.S researchers have gained new insights into how the small intestine repairs itself after the injury caused by intestinal rotavirus infection. Their findings have led them to propose that how the intestine repairs itself seems to depend on the type of damage, and they found that triggers are actually essential for repairing the virus-caused injury. The study appeared in Cell Reports.
"We studied a different damage model, damage caused by rotavirus, a common small intestinal viral infection that affects young children," said first author Winnie Zou, a student in the Medical Scientist Training Program in Dr. Mary Estes' lab at Baylor.
Repair and turnover of the epithelium, the most external cellular layer of the small intestine responsible for absorption of nutrients and other functions, depend on the intestinal stem cells, regardless of the cause of the damage.
There are two types of intestinal stem cells: CBCs (crypt-based columnar cells) and reserve intestinal stem cells. The type of injuries studied until now damages the highly proliferative CBCs, and when these stem cells are destroyed, the reserve intestinal stem cells respond to restore the damage. The response to injury caused by rotavirus, however, is different.
"Rotavirus is an infection and has a very specific damage pattern," Zou said. "The virus specifically infects epithelial cells, but not the stem cells. Because the stem cells are intact, we wanted to investigate the type of repair response that would restore the epithelium destroyed by the virus."
"Nobody had looked at this situation before," said senior author Dr. Mary Estes, Cullen Foundation Endowed Professor Chair of Human and Molecular Virology in molecular virology and microbiology at Baylor. "This is the first study of mammalian intestinal epithelial cell injury in which the stem cells are not damaged."
"Previous studies had shown that when CBC stem cells are damaged, the reserve stem cells come to their rescue leading the reconstitution of the damaged epithelium. When rotavirus damages the epithelium, but not the stem cells, we found that the CBCs, not the reserve stem cells, are the primary cell type involved in the restoration of the intestinal epithelium," said Zou.
"Until now, CBCs were not considered important for the repair of intestinal epithelium, but our results show that they are crucial for injury repair after rotavirus-induced epithelial cell damage in contrast to previous studies supporting the reserve intestinal stem cells as the cell type involved in epithelial restitution," said Estes.
The second unexpected finding refers to the source of the signaling molecules — called WNTs — that trigger the growth and activation of stem cells leading to injury repair. Scientists have described two sources of WNT molecules, epithelial cells and mesenchymal cells.
Until now, research has considered the mesenchymal and the epithelial WNT to be redundant and not essential on their own. "We found that the epithelial WNT molecules were essential to signal the stem cells to repair the damage caused by rotavirus infection," said Zou.
"I think this finding will be exciting for intestinal stem cell researchers. Now, we are exploring what the infection is doing that triggers WNT production in the epithelium," said Estes, who is also a member of the Dan L Duncan Comprehensive Cancer Center.