Hyaluronan metabolism enhanced during epidermal differentiation is suppressed by vitamin C3. (15th May 2018)

• Record Type: Journal Article
• Authors: Hämäläinen, L.; Kärkkäinen, E.; Takabe, P.; Rauhala, L.; Bart, G.; Kärnä, R.; Pasonen‐Seppänen, S.; Oikari, S.; Tammi, M.I.; Tammi, R.H.
• Is Part Of: British journal of dermatology. Volume 179:Number 3(2018)
• Page Start: 651
• Page End: 661
• Publication Date: 2018-05-15
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.16423
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: Hyaluronan is a large, linear glycosaminoglycan present throughout the narrow extracellular space of the vital epidermis. Increased hyaluronan metabolism takes place in epidermal hypertrophy, wound healing and cancer. Hyaluronan is produced by hyaluronan synthases and catabolized by hyaluronidases, reactive oxygen species and KIAA1199. Objectives: To investigate the changes in hyaluronan metabolism during epidermal stratification and maturation, and the impact of vitamin C on these events. Methods: Hyaluronan synthesis and expression of the hyaluronan‐related genes were analysed during epidermal maturation from a simple epithelium to a fully differentiated epidermis in organotypic cultures of rat epidermal keratinocytes using quantitative reverse transcriptase polymerase chain reaction, immunostaining and Western blotting, in the presence and absence of vitamin C. Results: With epidermal stratification, both the production and the degradation of hyaluronan were enhanced, resulting in an increase of hyaluronan fragments of various sizes. While the mRNA levels of Has3 and KIAA1199 remained stable during the maturation, Has1, Has2 and Hyal2 showed a transient upregulation during stratification, Hyal1 transcription remained permanently increased and transcription of the hyaluronan receptor, Cd44, decreased. At maturation, vitamin C downregulated Has2, Hyal2 and Cd44, whereas it increased high‐molecular‐mass hyaluronan in the epidermis, and reduced small fragments in the medium, suggesting stabilization of epidermal hyaluronan. Conclusions: Epidermal stratification and maturation is associated with enhanced hyaluronan turnover, and release of large amounts of hyaluronan fragments. The high turnover is suppressed by vitamin C, which is suggested to enhance normal epidermal differentiation in part through its effect on hyaluronan. Abstract : What's already known about this topic? The extracellular matrix polysaccharide hyaluronan is abundant in human epidermis and plays an important role in skin homeostasis and wound healing. Epidermis contains high levels of reactive oxygen species, which can induce hyaluronan degradation. What does this study add? Hyaluronan metabolism is activated during epidermal stratification but stabilized again upon maturation. A large part of hyaluronan exists as fragments, which may have signalling functions. Vitamin C further stabilized epidermal hyaluronan by suppressing both synthesis and degradation, which is suggested to contribute to normal differentiation. What is the translational message? Insults to epidermal homeostasis, such as trauma, inflammation and ultraviolet radiation, activate hyaluronan turnover, which maintains an inflammatory state. The present data show that by slowing down hyaluronan turnover, vitamin C has potential as a suppressor of epidermal inflammation. Linked Comment: Passi. Br J Dermatol 2018;179 :558–559 . Plain language summary available online Respond to this article