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저자： 업로드：2016-05-20 조회수：
Inflammatory bowel disease (IBD), of which Crohn's disease and ulcerative colitis are the main types, is on the increase in the United States, affecting more than 1.6 million people and explaining perhaps the increase in advertisements offering treatments and cures. Another intestinal disease is colon cancer, a leading cause of death, which is linked to diet and one's genetic predisposition to the disease.
Scientists at the University of California, Riverside have determined the distribution of the P1 and P2 isoforms of hepatocyte nuclear factor 4α (HNF4α) in the colons of mice. They report ("Opposing Roles of Nuclear Receptor HNF4α Isoforms in Colitis and Colitis-Associated Colon Cancer") in eLife that maintaining a balance of P1 and P2 is crucial for reducing risk of contracting colon cancer and colitis.
What is already known in the field of cell biology is that the HNF4α transcription factor plays a key role in both diseases. HNF4α comes in two major isoforms, P1-HNF4α and P2-HNF4α (P1 and P2), but just how each isoform is involved in colitis and colon cancer is not understood.
"P1 and P2 have been conserved between mice and humans for 70 million years," said Frances M. Sladek, Ph.D., professor of cell biology, who led the research project. "Both isoforms are important and we want to keep an appropriate balance between them in our gut by avoiding foods that would disrupt this balance and consuming foods that help preserve it. What these foods are is our next focus in the lab."
The intestine is the only adult tissue in the body that expresses both P1 and P2. Dr. Sladek and her team have shown for the first time that these isoforms perform nonredundant functions in the intestine and are relevant to colitis and colitis-associated colon cancer.
"Our study also suggests that finding a drug to stabilize one isoform should be more effective than targeting both isoforms for treating colitis and colon cancer," said Karthikeyani Chellappa, Ph.D., the first author of the research paper and a former postdoctoral researcher in Sladek's lab.
Dr. Sladek explained that the colonic epithelial surface has finger-like invaginations (into the colonic wall) called colonic crypts that house stem cells at their base. These stem cells help regenerate new epithelial cells that continuously migrate up toward the surface, thus ensuring complete renewal of the intestinal lining every 3–5 days.
The researchers observed that
the P1-positive cells were found in the surface lining and the top portion of
the crypt (green in the accompanying image) whereas P2-positive cells were
mostly in the proliferative compartment in the lower half of the crypt (the
proliferation marker is red in the im
