Aquaporins Are One of the Critical Factors in the Disruption of the Skin Barrier in Inflammatory Skin Diseases

Abstract

The skin is the largest organ of the human body, serving as an effective mechanical barrier between the internal milieu and the external environment. The skin is widely considered the first-line defence of the body, with an essential function in rejecting pathogens and preventing mechanical, chemical, and physical damages. Keratinocytes are the predominant cells of the outer skin layer, the epidermis, which acts as a mechanical and water-permeability barrier. The epidermis is a permanently renewed tissue where undifferentiated keratinocytes located at the basal layer proliferate and migrate to the overlying layers. During this migration process, keratinocytes undertake a differentiation program known as keratinization process. Dysregulation of this differentiation process can result in a series of skin disorders. In this context, aquaporins (AQPs), a family of membrane channel proteins allowing the movement of water and small neutral solutes, are emerging as important players in skin physiology and skin diseases. Here, we review the role of AQPs in skin keratinization, hydration, keratinocytes proliferation, water retention, barrier repair, wound healing, and immune response activation. We also discuss the dysregulated involvement of AQPs in some common inflammatory dermatological diseases characterised by skin barrier disruption.

The Multifaceted Role of Aquaporin-9 in Health and Its Potential as a Clinical Biomarker

“…The presence (cellular and subcellular localization) and role of AQP9 in the brain have been matter of discussions [58], with arguments of putative species differences and the very limited population of neurons in which this AQP seems to be expressed [85]. Cell differentiation [23][24][25]75] Male reproductive tract (m, r)…”

“…Less defined is the role played by AQP9 in the other tissues where this aquaglyceroporin/peroxiporin is expressed. In the stratum granulosum of the epidermis, a skin layer where tight junctions act as a paracellular barrier against small molecules, AQP9 was suggested to represent a transcellular route for the movement of solutes of biological relevance, such as glycerol and urea, into and out of the skin, and be involved in the terminal differentiation of keratinocytes [ 23 , 24 , 25 , 75 ]. In the principal cells of the epididymis and vas deferens, AQP9 is thought to have implications in sperm concentration and storage, respectively [ 54 ].…”

“…Through analysis of Aqp knockout (KO) mice phenotype and the effects of their up- or down-regulation at the cellular level, other additional important roles have been uncovered. Classical AQPs are key regulators in several physiological functions such as water reabsorption and urine concentration in kidney [ 17 ] and brain water homeostasis [ 18 ], while aquaglyceroporins are crucial for glycerol metabolism, energy homeostasis [ 19 , 20 , 21 ], oxidative stress [ 22 ], and skin hydration [ 23 , 24 ]. Superaquaporins have been pointed as important cellular entities for organelle homeostasis, such as supporting endoplasmic reticulum function [ 14 ].…”

Poria cocos Extract from Mushrooms Stimulates Aquaporin-3 via the PI3K/Akt/mTOR Signaling Pathway

“…23 , 24 In similar, AQP2 is mainly expressed on kidney and fibroblasts, 25 and rarely detected in keratinocytes. 5 , 26 , 27 Because AQP1 and AQP2 is rarely detected in keratinocytes, we think that the AQP1 was not detected well in our study. However, EPC significantly up-regulated the AQP3 in keratinocytes, which suggests that it may facilitate the transport and metabolism of water and glycerol in the skin epidermis, and the function of the epidermal water permeability barrier.…”

“…Aquaporins (AQPs), also called water channels, are a family of transmembrane proteins that mainly transport water across biological membranes and are involved in many physiological functions, including renal water balance, epithelial fluid secretion, cell migration, brain oedema and metabolism in adipocytes. 5 , 6 Among them, several of the mammalian aquaporins such as AQP1, and AQP2 appear to be highly selective for the passage of water, whereas others (recently termed aquaglyceroporins such as AQP3, AQP7 and AQP9) also transport glycerol. 7 Especially, AQP3, an aquaglyceroporin, is most abundantly expressed in keratinocytes of the basal layer of the human epidermis and is associated with keratinocyte migration, and proliferation.…”