Enhancement of elastin expression by transdermal administration of sialidase isozyme Neu2

Akira Minami,Kosei Fujita,Samir Mitragotri,Yasunori Iwao,Ayano Iuchi,Takashi Suzuki,Jun Goto,Tadamune Otsubo,Hiroaki Kanazawa,Ami Ishii,Yuka Fujita,Yuuki Kurebayashi,Tadanobu Takahashi,Mako Shiratori,Kiyoshi Ikeda,Yasuyo Mikami

doi:10.1038/s41598-021-82820-1

Akira Minami, Kosei Fujita + Show 14 more

Open Access

https://doi.org/10.1038/s41598-021-82820-1

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Abstract

Reduction of elastin in the skin causes various skin diseases as well as wrinkles and sagging with aging. Sialidase is a hydrolase that cleaves a sialic acid residue from sialoglycoconjugate. Cleavage of sialic acid from microfibrils by the sialidase isozyme Neu1 facilitates elastic fiber assembly. In the present study, we showed that a lower layer of the dermis and muscle showed relatively intense sialidase activity. The sialidase activity in the skin decreased with aging. Choline and geranate (CAGE), one of the ionic liquids, can deliver the sialidase subcutaneously while maintaining the enzymatic activity. The elastin level in the dermis was increased by applying sialidase from Arthrobacter ureafaciens (AUSA) with CAGE on the skin for 5 days in rats and senescence-accelerated mice prone 1 and 8. Sialidase activity in the dermis was considered to be mainly due to Neu2 based on the expression level of sialidase isozyme mRNA. Transdermal administration of Neu2 with CAGE also increased the level of elastin in the dermis. Therefore, not only Neu1 but also Neu2 would be involved in elastic fiber assembly. Transdermal administration of sialidase is expected to be useful for improvement of wrinkles and skin disorders due to the loss of elastic fibers.

Highlights

Reduction of elastin in the skin causes various skin diseases as well as wrinkles and sagging with aging
In the course of staining with BTP3-Neu5Ac in mammalian tissues, we newly found that the dermis has an intense sialidase activity in the skin
In skin damaged by prolonged sunlight exposure, amorphous elastin-containing material is accumulated in the upper dermis and results in a lack of r esilience[8,9,10]

Summary

Introduction

Reduction of elastin in the skin causes various skin diseases as well as wrinkles and sagging with aging. Abbreviations AUSA Sialidase from Arthrobacter ureafaciens BTP3-Neu5Ac Benzothiazolylphenol-based sialic acid derivative type 3 CAGE Choline and geranate DMSO-d6 Dimethyl sulfoxide-d6 EBP Elastin-binding protein PBS Phosphate-buffered saline SAM Senescence-accelerated mouse SAMP Senescence-prone 4MU-Neu5Ac 4-Methylumbelliferyl-α-D-N-acetylneuraminic acid. While staining various tissues with a BTP3-Neu5Ac, we previously revealed the distributions of sialidase activity in the brain and p ancreas[3,4]. Based on this information, we have found that sialidase is involved in memory processing and the regulation of Scientific Reports | (2021) 11:3302. In the course of staining with BTP3-Neu5Ac in mammalian tissues, we newly found that the dermis has an intense sialidase activity in the skin. Elastin turnover takes a long time, making it difficult to regenerate lost e lastin[14,15]

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Conclusion