Hyaluronan is a key regulator of skin homeostasis and wound healing

The study published by Hämäläinen et al.1 in this issue of the BJD addresses a very intriguing aspect of hyaluronan metabolism. A large body of evidence supports the critical role of this polymer in different tissues both in physiological conditions and in pathology.2, 3 Basically, two key aspects of the biological role of hyaluronan in tissues are fundamental: concentration and molecular size. The concentration of hyaluronan depends on a very finely tuned system that involves cell metabolism in several ways, ranging from energy level to genetic and epigenetic control of the expression of the three hyaluronan synthases. Hyaluronan size is strongly dependent on the degradation that is achieved through the activities of different hyaluronidases and by the action of reactive oxygen species (ROS). From this point of view the antioxidant activity in tissues could play a direct role in hyaluronan degradation, altering the efficiency of polymer degradation. The biological relevance of this situation depends on the fact that the hyaluronan fragments exert several important biological functions. For this reason, the hyaluronan fragments can be included in the family of matrikines, the biologically active fragments of the extracellular matrix. The relevance of hyaluronan metabolism in the skin is critical as it is particularly abundant in the dermis and epidermis. In the epidermis, considering the space available between keratinocytes and the amount of hyaluronan between these cells, the concentration reaches remarkably high levels, representing a key element in the epidermal structure. Therefore, it is not surprising that hyaluronan metabolism in the epidermis could regulate maturation of the tissue. The authors take advantage of the in vitro method developed by Tammi et al. by using rat keratinocyte organotypic cultures, which currently represents the most powerful and reproducible system with which to study epidermal development.4 It is easily evident that during cell stratification the metabolism of hyaluronan changes and the polymer disappears in the stratum corneum. Hyaluronidases and ROS are responsible for the degradation of hyaluronan, resulting in an increase of hyaluronan fragments which have several biological functions, not completely understood in skin, including the production of beta‐defensin 2.5 Vitamin C is an ROS scavenger and this study shows its possible role in hyaluronan stabilization, altering hyaluronan degradation and also influencing its production. Considering the increasing body of literature supporting the critical role of hyaluronan in skin, the concepts emerging from the data presented by Hämäläinen et al.1 are very important, indicating that hyaluronan is a key regulator of skin homeostasis and wound healing, opening the field to new speculation on the possibility of addressing hyaluronan metabolism in skin disease with a new therapeutically effective strategy.The relevance of hyaluronan metabolism in the skin is critical as it is particularly abundant in the dermis and epidermis. In the epidermis, considering the space available between keratinocytes and the amount of hyaluronan between these cells, the concentration reaches remarkably high levels, representing a key element in the epidermal structure