Accelerated human epidermal turnover driven by increased hyaluronan production. Issue 2 (February 2021)

• Record Type: Journal Article
• Authors: Endo, Yoko; Yoshida, Hiroyuki; Ota, Yukiko; Akazawa, Yumiko; Sayo, Tetsuya; Hanai, Ushio; Imagawa, Kotaro; Sasaki, Masashi; Takahashi, Yoshito
• Is Part Of: Journal of dermatological science. Volume 101:Issue 2(2021)
• Page Start: 123
• Page End: 133
• Publication Date: 2021-02
• Subjects: BPE bovine pituitary extract -- dsDNA double strand DNA -- ELISA enzyme-linked immunosorbent assay -- EGF epidermal growth factor -- FLG filaggrin -- GlcUA glucuronic acid -- H&E hematoxylin and eosin -- HA hyaluronan -- HABP HA binding protein -- HAS HA synthase -- KGF keratinocyte growth factor -- NAG N-acetylglucosamine -- β-NAG2 1-ethyl-β-N-acetylglucosaminide -- PBS phosphate buffered-saline -- PCNA proliferating cell nuclear antigen -- PUGNAc o-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino N-phenyl carbamate -- RPLP0 ribosomal protein lateral stalk subunit P0 -- siRNA small interfering RNA -- TGM1 transglutaminase 1 -- UDP uridine diphosphate; Hyaluronan -- N-acetylglucosamine -- Keratinocyte -- Proliferation -- Differentiation; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2020.12.002
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: Hyaluronan (HA) is an essential component of extracellular matrix in the skin. 1-ethyl-β- N -acetylglucosaminide (β-NAG2) is a selective inducer of HA production. β-NAG2 increased epidermal HA and thickness in reconstructed human skin equivalents. Epidermal proliferation and differentiation were promoted via enhanced HA production. Epidermal HA production plays a key role in epidermal morphogenesis and homeostasis. Abstract: Background: Hyaluronan (HA) is an essential component of extracellular matrix in the skin, but its functions in the epidermis remain elusive. Objective: We examined the interaction of increased HA production mediated by 1-ethyl-β- N -acetylglucosaminide (β-NAG2), a newly developed highly selective inducer of HA production which is intracellularly converted to UDP- N -acetylglucosamine, a substrate of HA, with epidermal proliferation and differentiation. Methods: The amount, molecular size and epidermal tissue distribution of HA and expression of CD44, a cell surface receptor for HA, were analyzed in β-NAG2-treated organ cultured human skin, reconstructed human skin equivalents or cultured human skin keratinocytes. The relationship between HA and epidermal proliferation or differentiation was examined. Results: β-NAG2 significantly increased HA production in the epidermis of skin explants or skin equivalents without affecting molecular size of HA (>2000 kDa) or CD44 mRNA expression. Histochemical experiments revealed that β-NAG2 enhances HA signals in the basal to granular layers of the epidermis of skin equivalents, accompanying increased epidermal stratification. Immunohistochemical experiments demonstrated that signals of Ki67, transglutaminase 1 and filaggrin are increased in β-NAG2-treated skin equivalents, and these observations were confirmed by the data showing that mRNA expression of PCNA, transglutaminase 1 (TGM1) and filaggrin (FLG) is significantly up-regulated by β-NAG2 in skin equivalents. Importantly, blockade of HA production by inhibiting conversion of β-NAG2 to UDP-NAG abolished β-NAG2-mediated up-regulation of PCNA, TGM1 and FLG mRNA expression in cultured keratinocytes. Conclusion: These results suggest that increased epidermal HA production plays a key role in epidermal morphogenesis and homeostasis by accelerating keratinocyte proliferation and differentiation.