Controlling Cell Turnover in the Intestinal Lining
The lining of the intestine is the most rapidly-renewing tissue in the body. Routine shedding of epithelial cells from this lining is a key element of tissue turnover, and is thus essential to maintaining optimal health. Altered shedding is associated with multiple disorders, ranging from inflammatory bowel disease (IBD) to colorectal cancer.
“We found that, surprisingly, EGF suppresses shedding of epithelial cells in the intestine through a selective, MAPK-dependent signaling pathway,” said CHLA researcher Mark R. Frey, who is also an assistant professor of Pediatrics and Biochemistry at the Keck School of Medicine of the University of Southern California. His team used coordinated in vitro models (cell culture and 3-D culture systems) to study the effects of blocking MAPK pathways. Similar results were found in vivo, in a novel zebrafish model for intestinal epithelial shedding.
This insight could identify potential targets for correcting pathological shedding in diseases such as IBD.
Additional contributors to the study include first author Jennifer C. Miguel, Adrienne A. Maxwell, Jonathan J. Hsieh, Denise Al Alam, D. Brent Polk and Ching-Ling Lien, Children’s Hospital Los Angeles and USC Keck School of Medicine; and Lukas C. Harnisch and Alastair J.M. Watson, Norwich Medical School, University of East Anglia, Norwich, UK.
The study was supported by grants from the National Institutes of Health (R01DK095004, R01HL096121; R01DK056008 and R01DK54993); the Crohn’s and Colitis Foundation of America, the American Cancer Society; and Wellcome Trust.
About Children’s Hospital Los Angeles
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