Role of HYBID (Hyaluronan Binding Protein Involved in Hyaluronan Depolymerization), Alias KIAA1199/CEMIP, in Hyaluronan Degradation in Normal and Photoaged Skin.

Hiroyuki Yoshida,Yasunori Okada

doi:10.3390/ijms20225804

Hiroyuki Yoshida, Yasunori Okada

Open Access

https://doi.org/10.3390/ijms20225804

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Abstract

Photoaged skin is characterized clinically by apparent manifestations such as wrinkles and sagging, and histologically by an accumulation of abnormal elastin and a severe loss of collagen fibers in the dermis. Quantitative and qualitative alterations in elastin and collagens are considered to be responsible for the formation of wrinkles and sagging. However, since the integrity of elastin and collagen fibers in the dermis is maintained by their interactions with hyaluronan (HA) and a proteoglycan network structure, HA degradation may be the initial process, prior to the breakdown of the fibrillary components, leading to wrinkles and sagging in photoaged skin. We have recently discovered a new HA-degrading mechanism mediated by HYBID (hyaluronan binding protein involved in hyaluronan depolymerization), alias KIAA1199/CEMIP, in human skin fibroblasts, and examined the implication of HYBID for skin photoaging. In this review, we give an overview of the characteristics of HYBID and its prospective roles in HA turnover in normal skin and excessive HA degradation in photoaged skin. In addition, we describe our data on the inhibition of HYBID activity and expression by plant extracts in skin fibroblasts; and propose novel strategies to prevent or improve photoaging symptoms, such as skin wrinkling, by inhibition of HYBID-mediated HA degradation.

Highlights

The skin is a multifunctional organ that is continuously exposed to many biological and environmental factors
Since these data suggested the presence of a new HA-degrading mechanism independent of CD44 and HYAL2, or HYAL1, in skin fibroblasts, we carried out a comprehensive survey of candidate genes whose expression levels were paralleled with HA depolymerization activity, and found that knockdown of KIAA1199, which was originally reported as a deafness gene of unknown function [24], abrogates HA-degrading activity in normal human skin fibroblasts [15]
Photoaged skin displays prominent alterations in the reticular dermis, which is located under the papillary dermis, showing an accumulation of abnormal elastin and a severe loss of interstitial collagen fibers, and such quantitative and qualitative alterations of dermal extracellular matrix (ECM) proteins have been proposed as candidates for wrinkle- and sagging-formation factors [3,4,5,10,11]

Summary

Introduction

The skin is a multifunctional organ that is continuously exposed to many biological and environmental factors. Many biochemical and histological studies on photoaged skin have demonstrated massive accumulation of aberrant elastic material, and disorganized and damaged collagen fibers in the dermis. The skin showing these alterations is referred to as ‘solar elastosis’ [4,5,6]. We searched for new molecules related to HA degradation by microarray analysis, and found that KIAA1199 has a key role in the binding and depolymerization of HA in normal human skin fibroblasts [15] (see below for the details). We propose the hypothesis that inhibition of HYBID-mediated HA degradation would be a useful remedy to improve skin wrinkling

Diverse Properties and Rapid Turnover of HA in the Skin

Molecular Mechanism of HA Synthesis in Skin Fibroblasts

HA Degradation Mediated by Newly Discovered HYBID in Skin Fibroblasts

Molecular Function of HYBID Protein

Cellular Mechanism of HYBID-Mediated HA Degradation

Conclusions