Switching On Wound Healing
Scientists have identified a molecular “switch” that controls the migration of skin cells necessary for wounds to close and heal.
AsianScientist (Mar. 14, 2013) - Scientists have identified a molecular "switch" that controls the migration of skin cells necessary for wounds to close and heal. This discovery could pave the way for therapeutics to improve healing of chronic wounds.
When the skin is wounded, a healing response is quickly activated to close the wound. However, in patients with diseases such as diabetes, wounds heal very slowly, making them susceptible to infections that could lead to amputations.
Chronic wounds in diabetes patients are a major global health burden and the most common cause of lower extremity amputations. These non-healing wounds tend to affect the elderly and disabled patients, particularly those confined to a wheelchair or bed-bound. Unfortunately, chronic wounds are currently poorly understood and insufficiently treated.
The team of scientists from India's Jnana Sanjeevini Diabetes Center in Bangalore and Singapore's Institute of Medical Biology, led by Dr. Prabha Sampath, first identified a "micro-RNA" molecule, known as miR-198, as the most significant and consistently down-regulated miRNA following skin injury. miR-198 is encoded within an exon of a gene called follistatin-like 1 (FSTL1). This means that the information to express miR-198 and FSTL1 protein are found within a single "message" produced by the cell.
These two molecules have opposite roles: miR-198, found in unwounded skin, inhibits skin cell migration and wound healing. On the other hand, the FSTL1 protein is expressed after injury and promotes skin cell migration and wound healing.
Importantly, miR-198 and FSTL1 protein cannot be produced at the same time; when one is on the other is off. A regulatory switch dictates their expression, which controls the "see-saw" between inactive resting skin cells and migrating cells necessary for wound healing.
Publishing in the journal Nature, Dr. Sampath and team showed that healthy unwounded skin contained high levels of miR-198 but no FSTL1 protein. The scientists discovered that high levels of miR-198 prevent skin cell migration by suppressing several genes needed for different aspects of the wound healing process.
However upon injury, miR-198 was switched off in the wound by a signal from transforming growth factor β1 (TGF-β1). FSTL1 was then expressed, which increased the expression of skin migration genes, 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, levels of miR-198 remained high, which inhibited skin cell migration and wound healing. As expected, there was no FSTL1 protein expressed, indicating that the “switch” is defective in chronic wounds.
When asked about future plans, Dr. Sampath said,
"We hope to translate this research into improved patient outcomes. Modulating the defective switch using anti-miR-198 along with polypeptides of FSTL1 can lead to the development of a novel therapeutic strategy to accelerate wound healing especially in patients with chronic wounds. We are planning to work on this strategy with pharmaceutical companies."
The article can be found at: Sundaram GM et al. (2013) ‘See-saw’ expression of microRNA-198 and FSTL1 from a single transcript in wound healing.
Source: A*STAR; Photo: Jordandelion/Flickr/CC.
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