Small RNAs help skin wounds heal faster with minimal scarring, find scientists

A class of molecules playing a crucial role in the regulation of gene expression and other cellular processes can restore normal skin structure rather than producing a scar, a University of Manchester led study in mice and humans suggests.

The New findings in The American Journal of Pathology, published by Elsevier, mean microRNA-29s, a class of small RNAs, could benefit patients affected by large-area or deep wounds prone to dysfunctional scarring.

The findings offer hope for an eventual to solution to the global problem of non-healing wounds, thought to cost between £11.25 billion and  £16.5 billion per year.

Dr Svitlana Kurinna, from the University’s Division of Cell Matrix Biology and Regenerative Medicine, was lead investigator of the study.

She said: “We had data showing microRNAs can regulate skin growth. However, microRNAs do not code for proteins, so it wasn’t clear how such small molecules can make changes to the skin. We therefore studied underlying mechanisms that could be targeted to improve wound healing in the skin.”

There is already good understanding of the molecular events during early wound healing stages of inflammation and tissue formation, showing microRNAs are important factors in healing and may regulate functions in skin repair. However, the mechanisms underlying tissue remodeling are unclear.

Scientists studying wound healing in mice with microRNA-29 switched off have suggested the release of microRNA-29 targets promote wound healing by regulating skin regeneration.

We expected the removal of microRNA-29 would help outer layers of the skin to grow faster. But it was the deep matrix of the wound that actually showed an improvement, and that was tremendously exciting

Dr Svitlana Kurinna 

That is done by binding long RNAs -  molecules carrying instructions from our DNA to different parts of the cell to make proteins – which code for a structural protein of the skin called laminin C2 (LAMC2).

LAMC2 is a crucial part of the glue that holds our cells in place and helps maintain the integrity and structure of tissues throughout the body, restoring the normal skin structure.

In the Manchester study, the researchers found that wild type mice healed quite well, but the skin of transgenic mice devoid of microRNA-29 regenerated even better.

To understand the reasons, they conducted deep microscopic analysis of the transgenic wounds and observed deposition of Lamc2—usually found in one of the skin layers in wild mice—around blood vessels inside the wounds of microRNA-29–deficient transgenic mice.

The observation showed microRNA-29 may be inhibiting the expression of Lamc2, and deletion in the transgenic mice relieved the inhibition, resulting in faster wound healing. Importantly, in human wounds, the new areas of LAMC2 deposition was found in wound matrix around small blood vessels under regenerating wound.

Dr Kurinna said: “These processes are likely to be mediated by the removal of microRNA-29, which improves cell matrix adhesion - the way cells in our body stick to and interact with the network of proteins and other molecules that surrounds cells known as the extracellular matrix.

“Our results further suggest a link between LAMC2, improved creation of new blood vessels (angiogenesis), and re-epithelialization -   the body's way of closing a wound.

“We expected the removal of microRNA-29 would help outer layers of the skin to grow faster. But it was the deep matrix of the wound that actually showed an improvement, and that was tremendously exciting.”

The findings demonstrate the role of microRNA-29 in epidermal repair and suggest the release of microRNA-29 targets, particularly LAMC2, promotes wound healing.

That could mean the inhibition of microRNA-29 and/or overexpression of LAMC2 may be a new and effective strategy for improving wound healing.

Dr Kurinna added: “Our findings are of particular interest because they describe the mechanism which restores normal skin structure, rather than a wound closure by scar tissue. Any improvement of normal skin repair would therefore help many patients affected by large-area or deep wounds prone to dysfunctional scarring.”

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