Featured Research

from universities, journals, and other organizations

'Switch' critical to wound healing identified

Date:
March 8, 2013
Source:
Agency for Science, Technology and Research (A*STAR), Singapore
Summary:
Patients with diseases such as diabetes suffer from painful wounds that take a long time to heal making them more susceptible to infections that could even lead to amputations. A new discovery paves the way for therapeutics to improve healing of such chronic wounds, which are a significant burden to patients.

.Scientists from A*STAR's Institute of Medical Biology (IMB) have identified a molecular "switch" that controls the migration of skin cells necessary for wounds to close and heal. This is especially significant for diabetics and other patients who suffer from chronic wounds, wounds that do not heal or take years to do so, which are vulnerable to infections and could lead to amputations. This switch mechanism may hold the key to developing therapeutics that will reduce or prevent chronic wounds.

The scientists discovered that a tiny "micro-RNA" molecule, called miR-198, controls several different processes that help wound healing, by keeping them switched off in healthy skin. When skin is wounded, the manufacture of miR-198 quickly stops and the levels of miR-198 drop, switching on many wound healing processes.

In the non-healing wounds of diabetics, miR-198 does not disappear and wound healing remains blocked. This therefore identifies miR-198 as a potential diagnostic biomarker for non-healing wounds.

These findings were recently published in the journal Nature. The research leading to this discovery was carried out in collaboration with A*STAR's Bioinformatics Institute (BII), National University Hospital (NUH), Singapore and Jnana Sanjeevini Diabetes Center, Bangalore, India.

Importance of this discovery

Chronic wounds in patients with diabetes are a major global health burden and the most common cause of lower extremity amputations. In Singapore, diabetes is the fifth most common medical condition diagnosed and one in nine people aged 18 to 69 has diabetes. Unfortunately, chronic wounds are currently poorly understood and insufficiently treated. Chronic wounds also tend to affect the elderly and disabled patients, especially those confined to a wheelchair or bed-bound.

Dr. Prabha Sampath said, "Moving forward, we hope to translate this research into improved patient outcomes. We can now build on this research, to see how we can modulate the defective switch in chronic wounds by targeting miR-198 and its interacting molecules, to develop new strategies for treating chronic wounds."

Professor Birgitte Lane, Executive Director of IMB, said, "This switch appears to be an entirely new regulatory component in wound healing, and probably a very important one. Poor wound healing is a major healthcare burden, and this discovery is particularly timely in the face of aging populations and the sharp global rise in diabetes. The finding gives us a platform from which to develop therapies that could significantly reduce chronic wounds and improve healthcare."

An FSTL1-miR-198 molecular 'see-saw' switch

The information necessary to expressmicroRNA-198 (miR-198) and follistatin-like 1 (FSTL1) protein are found in a single "message" produced by the cell. However, miR-198 and FSTL1 protein cannot be produced at the same time -- it can only be one or the other. These two molecules also have opposite roles: miR-198 (found in unwounded skin) inhibits skin cell migration and wound healing, whereas FSTL1 protein (expressed after injury) promotes skin cell migration and wound healing. A regulatory switch dictates their expression, and hence controls the "see-saw" between inactive resting skin cells and the cell migration necessary for wound healing.

Dr. Sampath and her team showed that healthy unwounded skin contained high levels of miR-198 but no FSTL1 protein. They demonstrated that these high levels of miR-198 prevent skin cell migration by suppressing several genes, such as PLAU, LAMC2 and DIAPH1, which are needed for different aspects of the wound healing process. However upon injury, miR-198 is switched off in the wound by a signal from transforming growth factor β1 (TGF-β1). This allows FSTL1 to now be made instead, and the skin migration genes to be unblocked, promoting migration of skin cells into the wound area to drive skin wound healing.

The scientists further examined skin samples of chronic non-healing ulcer wounds from patients with diabetes mellitus. They observed that, unlike healthy skin that had been injured, there remained high levels of miR-198 (inhibiting skin cell migration and wound healing) and an absence of FSTL1 protein (promoting skin cell migration upon wounding), indicating that this "switch" is defective in chronic wounds.


Story Source:

The above story is based on materials provided by Agency for Science, Technology and Research (A*STAR), Singapore. Note: Materials may be edited for content and length.


Journal Reference:

  1. Gopinath M. Sundaram, John E. A. Common, Felicia E. Gopal, Satyanarayana Srikanta, Krishnaswamy Lakshman, Declan P. Lunny, Thiam C. Lim, Vivek Tanavde, E. Birgitte Lane, Prabha Sampath. ‘See-saw’ expression of microRNA-198 and FSTL1 from a single transcript in wound healing. Nature, 2013; 495 (7439): 103 DOI: 10.1038/nature11890

Cite This Page:

Agency for Science, Technology and Research (A*STAR), Singapore. "'Switch' critical to wound healing identified." ScienceDaily. ScienceDaily, 8 March 2013. <www.sciencedaily.com/releases/2013/03/130308111307.htm>.
Agency for Science, Technology and Research (A*STAR), Singapore. (2013, March 8). 'Switch' critical to wound healing identified. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2013/03/130308111307.htm
Agency for Science, Technology and Research (A*STAR), Singapore. "'Switch' critical to wound healing identified." ScienceDaily. www.sciencedaily.com/releases/2013/03/130308111307.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
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