SMALL molecule that regulates gene expression performs a key role in progressing wounds through their healing stages, according to the results of a new study.
Wound healing is a complicated process that progresses in stages, and there are few targeted treatments available for when it fails. Current therapies for chronic wounds focus on controllable factors such as clearance of infections, and the study researchers have underlined the pressing need for treatments that go deeper and target the wound healing process directly. However, they have indicated that the identified molecule, called miR-132, may comprise a new target for the treatment of harder-to-treat, chronic wounds.
The study’s primary focus was on two stages of wound healing: the inflammatory stage, during which the immune cells expel debris such as damaged and dead cells and bacteria; and the proliferative stage, during which skin cells multiply to form new tissue. The shift between these stages is vital and may determine whether the wound heals successfully or not.
Following on from earlier studies, the researchers investigated a group of molecules called microRNAs (miRNAs), small pieces of genetic code that regulate the genes that hold instructions for making proteins. They gathered skin biopsies from the edge of wounds and looked for changes in miRNA expression during the healing process. The team found that one miRNA in particular, miR-132, was very active during the inflammatory stage in skin cells called epidermal keratinocytes, which form the outermost layer of the skin. They also observed how the molecule peaked in the subsequent proliferative stage.
During the inflammatory stage, miR-132 caused fewer immune cells to migrate to the wound, whereas a lack of miR-132 caused more immune cells to move to the wound and increase inflammation. During the proliferative stage, miR-132 promoted keratinocyte growth. Conversely, a lack of miR-132 restricted keratinocyte growth and slowed wound healing.
Principal investigator Dr Ning Xu Landén, Assistant Professor, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, said: “Our results show that miR-132 is important during the transition from the inflammatory to the proliferative phase and therefore acts as a critical regulator of skin wound healing. Due to its pro-healing capacity, miR-132 may be an attractive therapeutic target for chronic skin wounds. Our goal is to develop a microRNA-based treatment to promote healing.”