The discovery is thought to offer an introduction into new investigation on chronic digestive diseases, and may be able to lead to new findings on repairing damage and injuries in the digestive system. The research was first performed in mice and later reproduced in human cells.
The two most common inflammatory bowel diseases are ulcerative colitis and Crohn’s Disease, which affect about 1.5 million people in the U.S. alone. With these diseases, the body confuses cells in the intestine and attacks them, since there is an abnormal immune response. As a result, patients commonly suffer from chronic injuries to the colon, which is considered a risk factor for colon cancer. One way to develop therapeutic treatment may be understanding the cellular pathways involved.
MicroRNAs work as locks and regulate the amount of protein that is produced by the body, which defines how the body responds to the stimulus. Researchers have studied how the regulators function without abnormality and how it is affected by diseases such as cancer. About 500 to 1000 microRNAs were found to be encoded in the genomes of mammals.
“We identified a novel role for microRNAs in regulating wound healing in the intestine,” said Dr. Joshua Mendell, CPRIT Scholar in Cancer Research, Professor of Molecular Biology, and member of the UT Southwestern Harold C. Simmons Cancer Center. “This finding has important implications for diseases such as ulcerative colitis and Crohn’s disease and may be relevant to wound healing mechanisms in other tissues.”
Most of the published research literature on the subject focuses on the implications of microRNAs in colon cancer. On the contrary, little is known about the natural function of the colon. This five-year research, whose findings were published in the journal Cell, began by removing the gene that produces the microRNAs in mouse models, with investigators focusing on two microRNAs: miR-143 and miR-145.
The epithelial cells, which normally increase their growth to foster repair within the body, were not able to replicate when under stress, according to the results. “The epithelial cells of the colon normally proliferate quickly to fill in the wounds from an injury. Without these microRNAs, the epithelial cells are unable to switch into this repair mode, so they never heal the wounds and the mice are not able to survive,” Dr. Guanglu Shi, postdoctoral researcher in Molecular Biology, explained. Research revealed that cells lined the intestines and separated the content from the rest of the body, absorbing the needed nutrients.
The new research also reopens a longstanding debate over where exactly microRNAs are located, since the investigators discovered that they dwell in supporting cells, called mesenchymal cells, and not in epithelial cells as originally thought. “This was surprising because colon cancers derive from the epithelial cells, so it was assumed that the microRNAs must function within them,” Dr. Mendell said. “If these microRNAs do participate in colon cancer, they must do so by acting from outside the epithelium.”
Studying the accurate location of the microRNAs is crucial to understanding the pathways that regulate it and may even eventually determine if they can be manipulated for therapeutic purposes.
Dr. Mendell’s team worked in partnership with a group of surgeons from UT Southwestern, including Dr. Joselin Anandam, Assistant Professor of Surgery, Dr. Abier Abdelnaby, Assistant Professor of Surgery, Dr. Glen Balch, Assistant Professor of Surgery, and Dr. John Mansour, Assistant Professor of Surgery, and Dr. Adam Yopp, Assistant Professor of Surgery.
UT Southwestern’s Harold C. Simmons Cancer Center is the only National Cancer Institute in North Texas and one of the 66 in the entire country. The investigations include 13 major cancer care programs, which seek to develop both innovative treatments and patient care and prevention techniques.