Featured Research

from universities, journals, and other organizations

Wound-healing role for microRNAs in colon offer new insight to inflammatory bowel diseases

Date:
May 23, 2014
Source:
UT Southwestern Medical Center
Summary:
A microRNA cluster believed to be important for suppressing colon cancer has been found to play a critical role in wound healing in the intestine, cancer researchers have found. The findings, first discovered in mice and later reproduced in human cells, could provide a fresh avenue for investigating chronic digestive diseases and for potentially repairing damage in these and other disease or injury settings.

This is Dr. Joshua Mendell, UT Southwestern Medical Center.
Credit: UT Southwestern

A microRNA cluster believed to be important for suppressing colon cancer has been found to play a critical role in wound healing in the intestine, UT Southwestern cancer researchers have found.

The findings, first discovered in mice and later reproduced in human cells, could provide a fresh avenue for investigating chronic digestive diseases and for potentially repairing damage in these and other disease or injury settings.

"We identified a novel role for microRNAs in regulating wound healing in the intestine. 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.

Ulcerative colitis and Crohn's disease -- the two most common inflammatory bowel diseases affecting an estimated 1.5 million in the U.S. -- stem from an abnormal immune response, which results in the body mistakenly attacking cells in the intestine. The resulting chronic injury to the colon also is considered a risk factor for colon cancer. Understanding the cellular pathways involved could eventually lead to potential therapeutic treatments.

MicroRNAs serve as brakes that help regulate how much of a protein is made, which, in turn, determines how cells respond to various stimuli. Approximately 500 to 1000 microRNAs are encoded in the genomes of mammals. Dr. Mendell's laboratory studies how these tiny regulators work normally and how diseases such as cancer arise when they function in an abnormal manner.

These latest findings, which appear in the journal Cell, focus on two microRNAs: miR-143 and miR-145. While there is extensive literature implicating these microRNAs in colon cancer, little is known about their natural function in the colon. So Dr. Guanglu Shi, postdoctoral researcher in Molecular Biology, and other researchers began their five-year investigation by removing or "knocking out" the gene that produces these two microRNAs in mouse models.

The researchers found that the cells that normally increase their growth to make repairs, called epithelial cells, fail under stress in the knockout animals. Epithelial cells line the intestines where food is digested, separating the contents from the rest of the body and absorbing needed nutrients.

"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.

In addition, the research upended traditional thinking about where the tiny microRNAs reside, discovering to everyone's surprise that they reside in supporting cells, called mesenchymal cells, instead of the epithelial cells themselves as 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. "If these microRNAs do participate in colon cancer, they must do so by acting from outside the epithelium."

Identifying the accurate location of the microRNAs is essential to locating the pathways they regulate and eventually, to determining whether they can be manipulated for therapeutic purposes.

Dr. Mendell's team collaborated with a group of surgeons at 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, who provided human tissue specimens. "The ability to work closely with an outstanding clinical team enabled us to confirm that our findings in mice extend to humans," Dr. Mendell said.

In addition, the researchers say they have worked out one of the many pathways regulated by these microRNAs, called the insulin-like growth factor signaling pathway.

"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."

Knocking out miR-143 and miR-145 counteracts that effect.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. RaghuR. Chivukula, Guanglu Shi, Asha Acharya, EricW. Mills, LaurenR. Zeitels, JoselinL. Anandam, AbierA. Abdelnaby, GlenC. Balch, JohnC. Mansour, AdamC. Yopp, Anirban Maitra, JoshuaT. Mendell. An Essential Mesenchymal Function for miR-143/145 in Intestinal Epithelial Regeneration. Cell, 2014; 157 (5): 1104 DOI: 10.1016/j.cell.2014.03.055

Cite This Page:

UT Southwestern Medical Center. "Wound-healing role for microRNAs in colon offer new insight to inflammatory bowel diseases." ScienceDaily. ScienceDaily, 23 May 2014. <www.sciencedaily.com/releases/2014/05/140523145350.htm>.
UT Southwestern Medical Center. (2014, May 23). Wound-healing role for microRNAs in colon offer new insight to inflammatory bowel diseases. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2014/05/140523145350.htm
UT Southwestern Medical Center. "Wound-healing role for microRNAs in colon offer new insight to inflammatory bowel diseases." ScienceDaily. www.sciencedaily.com/releases/2014/05/140523145350.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins