Aquaporin-3 in the epidermis: more than skin deep

Abstract

The skin is essential for terrestrial life. It is responsible for regulating water permeability and functions as a mechanical barrier that protects against environmental insults such as microbial infection, ultraviolet light, injury, and heat and cold, which could damage the cells of the body and compromise survival of the organism. This barrier is provided by the outer layer, the epidermis, which is composed predominantly of keratinocytes; keratinocytes undergo a program of differentiation to form the stratum corneum comprising the cornified squame “bricks” and lipid “mortar.” Dysregulation of this differentiation program can result in skin diseases, including psoriasis and nonmelanoma skin cancers, among others. Accumulating evidence in the literature indicates that the water-, glycerol-, and hydrogen peroxide-transporting channel aquaporin-3 (AQP3) plays a key role in various processes involved in keratinocyte function, and abnormalities in this channel have been observed in several human skin diseases. Here, we discuss the data linking AQP3 to keratinocyte proliferation, migration, differentiation, and survival as well as its role in skin properties and functions like hydration, water retention, wound healing, and barrier repair. We also discuss the mechanisms regulating AQP3 levels, localization, and function and the anomalies in AQP3 that are associated with various skin diseases.

Role of Cutaneous Aquaporins in the Development of Xeroderma in Type 2 Diabetes

“…The dermal water content was reported to be decreased in AQP3-knockout mice [7]. In addition, cutaneous AQP3 is known to change in various skin disorders [25]; for example, AQP3 is decreased in psoriasis [26] and vitiligo [27,28] and during aging [29], causing skin dryness. Furthermore, it was recently found that a decrease in skin AQP3 was involved in the dry skin observed upon treatment with an epidermal growth factor receptor (EGFR) inhibitor [30].…”

Human Aquaporins: Functional Diversity and Potential Roles in Infectious and Non-infectious Diseases

“…Six AQPs are found in the skin, which are distributed to epidermis (AQP1, 3, 7, and 10), dermis (AQP1, 3, and 5), and hypodermis (AQP7) ( Patel et al, 2017 ). Skin AQPs are associated with skin hydration, cell proliferation and differentiation, migration, immunity, and wound healing ( Boury-Jamot et al, 2009 ; Sebastian et al, 2015 ; Bollag et al, 2020 ). Specifically, AQP3 is involved in epidermal cell proliferation and migration; AQP1 controls water movement between blood and dermis to maintain hydration; AQP5, found in both epical and basolateral membranes of the sweat gland is involved in water secretion; AQP7 plays important role to release glycerol from adipocytes for energy production and AQP9 facilitates the transport of glycerol, urea, and H 2 O 2 for defense mechanism ( Patel et al, 2017 ).…”

“…Down-regulation and/or mislocalization of AQP3, the most abundant and largely studied aquaglyceroporin in the skin, are associated with psoriasis ( Lee et al, 2012 ; Patel et al, 2017 ; Bollag et al, 2020 ) and vitiligo ( Kim and Lee, 2010 ; Esmat et al, 2018 ). However, although some studies have reported increased mRNA levels of AQP3 in proliferating keratinocytes in psoriasis ( Bowcock et al, 2001 ; Swindell et al, 2014 ), its expression is down-regulated with later differentiation of keratinocytes ( Zheng and Bollinger Bollag, 2003 ).…”

“…The up-regulation of AQP3 both in mRNA and protein levels has been demonstrated in atopic dermatitis lesions or eczema in human patients and mouse models ( Olsson et al, 2006 ; Nakahigashi et al, 2011 ). The down-regulation of AQP3 is supposed to be associated with xeroderma observed in diabetes because streptozotocin-induced diabetic mice showed decreased levels of AQP3 with reduced dermal water content ( Ikarashi et al, 2017 ; Bollag et al, 2020 ). Recent studies demonstrated that down-regulation of AQP3 might be involved in some other skin diseases such as bullous pemphigus ( Korany et al, 2019 ) and symmetrical acrokeratoderma ( Rong et al, 2019 ); however, it’s up-regulation might be involved in scleroderma/systemic sclerosis ( Luo et al, 2016 ).…”

Dietary Collagen Hydrolysates Ameliorate Furrowed and Parched Skin Caused by Photoaging in Hairless Mice

“…Accordingly, chronic UV-B irradiation results in loss of hyaluronic acid from the epidermis, thereby contributing to the quiescent phenotype of epidermal keratinocytes. The water- and glycerol-transporting protein AQP3 in the viable epidermis is involved in the mechanisms responsible for various keratinocyte functions including proliferation, hydration, water retention, and barrier function [ 25 , 30 , 33 ]. Various abnormalities in this channel are observed in several skin diseases such as psoriasis and skin cancers [ 33 ].…”