A Protein Released by Intestinal Cells Helps Regulate the Composition of the Lining of the Gut

BACKGROUND 

The gastrointestinal tract includes the organs that digest food, absorb nutrients and process the body’s waste. A protein called mucin is essential to the proper functioning of these organs, which are basically a long, coiled tube. When combined with water, mucin forms mucus, a slippery substance that lubricates the gut’s lining. Mucus creates a sticky barrier that catches and traps harmful particles. 

When the body produces too much or too little mucin, the result can be unhealthy levels of bacteria, trouble digesting food and absorbing nutrients, and other issues. By better understanding the cellular and molecular processes involved in mucus formation, scientists aim to uncover how to treat gastrointestinal-related diseases. 

FINDINGS

Because of this study, investigators now have a better understanding of how mucin is created and regulated. The epithelium, the type of tissue that covers internal and external surfaces on the body, is made up of cells that produce a protein called tumor necrosis factor (TNF). Investigators learned that this protein contributes to cell differentiation and communication that result in a healthy balance of mucin production and turnover.  

METHODS

Investigators observed the effect of removing TNF from laboratory mice and examined tissue samples from people with inflammatory bowel disease on anti-TNF therapy. A lack of TNF led to an increased number of cells called goblet cells that produce mucin. The absence of TNF also resulted in mucus accumulation, unhealthy bacterial levels and slower gut movement. 

IMPACT

“Epithelial TNF is a vital regulator of mucin production, and when this process is optimal, it contributes to a healthy gastrointestinal tract,” said Ophir Klein, MD, PhD, executive director of Cedars-Sinai Guerin Children’s, the David and Meredith Kaplan Distinguished Chair in Children’s Health and a corresponding author of the study. “With these findings, we can study how to manipulate mucin production to treat diseases of the gastrointestinal tract.”

AUTHORS

Efren A. Reyes, PhD, University of California, San Francisco; David Castillo-Azofeifa, PhD, University of California, San Francisco, and Genentech, Inc.; Jérémie Rispal, PhD, University of California, San Francisco; Tomas Wald, PhD, University of California, San Francisco; Rachel Zwick, PhD, University of California, San Francisco; Brisa Palikuqi, PhD, University of California, San Francisco; Angela Mujukian, MD, Cedars-Sinai; Shervin Rabizadeh, MD, MBA, Cedars-Sinai; Alexander R. Gupta, MD, University of California, San Francisco; James M. Gardner, MD, PhD, University of California, San Francisco; Dario Boffelli, PhD, Cedars-Sinai; Zev J. Gartner, PhD, University of California, San Francisco; Ophir Klein, MD, PhD, Cedars-Sinai.

FUNDING

This research was supported in part by the National Institutes of Health, the Center for Cellular Construction and a UCSF/NIGMS IMSD Fellowship.