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Science & Technology, UK (Commonwealth Union) – A recent study led by the University of Manchester has discovered that a class of molecules, microRNA-29s, can significantly improve skin structure and potentially prevent scarring. The research, published in The American Journal of Pathology, reveals that these small RNA molecules could be a game-changer for patients with large-area or deep wounds prone to abnormal scarring. This groundbreaking discovery offers hope for an eventual solution to the worldwide issue of non-healing wounds, which is estimated to cost between £11.25 billion and £16.5 billion per year. Dr. Svitlana Kurinna, from the University of Manchester, Division of Cell Matrix Biology and Regenerative Medicine, served as the lead investigator of this promising study.
Dr. Kurinna says “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.”
MicroRNAs are small, non-coding RNA molecules, typically 20-24 nucleotides long, that play a crucial role in regulating gene expression. They are transcribed from the genome as longer precursors called primary microRNAs (pri-miRNAs), which are then processed by the nuclear enzyme Drosha to form shorter precursors called precursor microRNAs (pre-miRNAs). After being transported to the cytoplasm, pre-miRNAs are further processed by the enzyme Dicer into mature microRNAs. These mature microRNAs form a complex with the Argonaute protein, which is a key component of the RNA-induced silencing complex (RISC). The RISC complex then targets specific messenger RNA (mRNA) molecules for degradation or translational repression, thereby modulating the expression of target genes.
MicroRNAs have long been recognized as vital components in the early stages of wound healing, including inflammation and tissue formation. These small RNA molecules are known to regulate various functions in skin repair. However, the mechanisms behind tissue remodeling remain elusive. In a study conducted on mice with microRNA-29 disabled, researchers discovered that the release of microRNA-29 targets aids in wound healing by regulating skin regeneration. This process involves binding long RNAs – molecules that carry genetic instructions from DNA to different parts of the cell to produce proteins – which code for a structural protein of the skin called laminin C2 (LAMC2). LAMC2 is a critical element in the adhesion of cells and the maintenance of tissue integrity and structure throughout the body, ultimately restoring normal skin structure.
In the Manchester study, researchers discovered that wild type mice healed well, but transgenic mice lacking microRNA-29 experienced even better skin regeneration. To delve into the causes, they conducted a thorough microscopic analysis of the transgenic wounds and observed Lamc2 deposits, typically found in one of the skin layers in wild mice, around blood vessels within the wounds of microRNA-29-deficient transgenic mice. This observation suggested that microRNA-29 might be suppressing Lamc2 expression, and the deletion in transgenic mice alleviated the inhibition, leading to faster wound healing. Interestingly, in human wounds, new areas of LAMC2 deposition were found in the wound matrix around small blood vessels during regeneration. Dr. Kurinna indicated that, the procedures are likely to be mediated by taking away the microRNA-29, that improves cell-matrix sticking together- the way cells in our body adhere to and engage with 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 study shows that microRNA-29 plays a crucial part in mending the skin and implies that by suppressing microRNA-29 and/or boosting the production of LAMC2, a more efficient approach to healing wounds could be achieved.
Dr Kurinna further explained “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.”
As indicated in the research this deeply scientific techniques taking into account genetic procedural steps could provide valuable insights into the wound healing process.
