New insights into MicroRNAs role in healing could help treat Crohn's, colitis
UT Southwestern cancer researchers have found a new target for helping the colon heal. The finding could mean a new approach for treating inflammatory bowel disease like Crohn’s disease and ulcerative colitis.
Role of microRNAs discovered for healing the intestines
The researchers first discovered the role of microRNAs thought to lead to the development of colon cancer in mice that they subsequently reproduced in human cells.
“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," said Dr. Joshua Mendell, CPRIT Scholar in Cancer Research, Professor of Molecular Biology, and member of the UT Southwestern Harold C. Simmons Cancer Center.
New therapies for bowel disease
The hope is that the finding could eventually lead to therapeutic treatments for the bowel diseases that stem from autoimmune dysfunction and affects an estimated 1.5 million people in the United States. The discovery also gives new insights into how the intestines heal.
The scientists discovered two MicroRNAs that have a unique role that regulates production of a protein that in turn determines how cells respond to certain stimuli. Abnormal cell response can lead to injury and cancer.
The two microRNAs that the researchers focused on are miR-143 and miR-145 whose function in the colon was previously unknown.
Over a period of five-years Dr. Guanglu Shi, postdoctoral researcher in Molecular Biology, and colleagues began their five-year investigation by removed the gene that produces the two microRNAs in mice.
Without miR-143 and miR-145 epithelial cells in the colon can’t repair themselves.
"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. Shi said.
The researchers also found he MicroRNAs live in mesenchymal cells rather than epithelial cells that was previously 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 in a press release. "If these microRNAs do participate in colon cancer, they must do so by acting from outside the epithelium."
Knowing the location of the microRNAs means there is a way to find better treatment options for inflammatory bowel diseases. It also gives new insight into how the gut heals that was previously unknown.
"This pathway is involved in many different processes in the body, but one function is to stimulate wound healing responses," Dr. Mendell explained. "Increasing the amount of insulin-like growth factor signaling improves wound healing in the intestine." Eliminating miR-143 and miR-145 has the opposite effect of allowing the colon to stay inflamed and injured.
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