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Oligosaccharides of hyaluronic acid increased epidermal cell stemness by modulation of integrin expression


Correspondence: K.-C Park, MD, PhD, Department of Dermatology, Seoul National University Bundang Hospital, Gumi-ro 166 Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Korea. E-mail:



Hyaluronic acid (HA) is an abundant matrix component and is degraded into polymers of various sizes. These generated fragments appear to have properties that affect wound healing of the skin. In industry, small-sized HA is used as a moisturizing agent but can have biologic effects when it is absorbed through the skin with barrier disruption.


In this study, the regenerative effects of these molecules were investigated using skin equivalent (SE) models.


Normal human keratinocytes and fibroblasts were isolated, and the effects of oligosaccharides of HA were tested in cultured keratinocytes and in the SE model.


In the monolayer of cultured keratinocytes, oligosaccharides of HA did not affect the proliferation of keratinocytes. However, the epidermis became thicker when oligosaccharides of HA were added during the culture of SE models. The data also showed that oligosaccharides of HA promote the differentiation of the epidermis. Furthermore, the expression of p63, integrin-α6 and integrin-β1 was increased. Western blot analysis also showed increased expression of both integrins.


These findings suggest that oligosaccharides of HA increase the differentiation of the epidermis. In addition, increased number of p63, a putative stem cell marker of the skin, showed that oligosaccharides of HA promote the survival of basal stem cells by modulating the expression of integrin-α6 and integrin-β1. Finally, it can be said that inflammation-induced small-sized oligosaccharides can have beneficial effects on epidermal regeneration and topically applied oligosaccharide of HA can have healing effects in skin problems.

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