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.
Researchers at The Saban Research Institute of Children's Hospital Los Angeles (CHLA) looked at ways such shedding and cell regeneration are controlled in healthy intestine. Their study, currently published online by the Journal of Cell Science, showed that shedding is negatively regulated by epidermal growth factor (EGF) - an important driver of intestinal growth and differentiation.
"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
Children's Hospital Los Angeles has been named the best children's hospital in California and among the top 10 in the nation for clinical excellence with its selection to the prestigious U.S. News & World Report Honor Roll. Children's Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States. Children's Hospital is also one of America's premier teaching hospitals through its affiliation since 1932 with the Keck School of Medicine of the University of Southern California. For more information, visit CHLA.org. Follow us on Twitter, Facebook, YouTube and LinkedIn, or visit our blog at http://researchlablog.