Aquaporins in the practice of a cosmetologist

Alla Belovol, Ph.D., Associate Professor, Head of the Department of Dermatology, Venereology and Medical Cosmetology, Kharkov National Medical University (Ukraine, Kharkov)
Svetlana Tkachenko, Ph.D., Associate Professor, Department of Dermatology, Venereology and Medical Cosmetology, Kharkov National Medical University (Ukraine, Kharkov)

Water channels in organs and tissues

Skin hydration is an extremely important parameter for both dermatological and cosmetological practice. This is a summary concept determined by the consistency of the barriers that prevent water evaporation (lipid film, epidermal barrier), the functionality of the natural moisturizing factor, as well as the work of the structures that saturate the epidermis with moisture (dermis and microvasculature). However, there is another component of the epidermis that is involved in the redistribution of moisture and may play a role in the pathogenesis of dermatoses and cosmetic skin imperfections.

It is known that water can penetrate the lipid epidermal bilayer. In 2003, Peter Agre and Roderick MacKinnon received the Nobel Prize in Chemistry for the discovery of aquaporins (AQPs), substances that regulate water transport in tissues. These are membrane proteins that form water channels and facilitate the movement of water in various organs and tissues: kidneys, eye tissue, digestive tract, brain, and skin. A total of 13 forms of aquaporins are known in animals, which are classified as AQP 0-12. Functionally, they can be divided into two subtypes: AKP-1, -2, -4, -5 and -8, which transport only water, and AKP-3, -7, -9 and -10, which, in addition to water, can also carry other substances such as glycerol and urea.

It has recently become known that several types of aquaporins are present in human skin. Aquaporin-1 is found in the vascular endothelium of the dermis, dermal fibroblasts and melanocytes. Aquaporin-9 and -10 were detected in epidermal keratinocytes and monocytes. Preadipocytes contain aquaporin-9 and -7, sweat gland cells contain aquaporin-5. Aquaporins-3 (AQP-3) were also found in epidermocytes. The predominant aquaporins-3 in the human epidermis are permeable to water and glycerol.

Today it is believed that AKP-3 is the most significant for skin hydration. They were first discovered in the cytoplasmic membrane of human epidermal keratinocytes back in 1998. Aquaporins-3 are also called aquaglyceroporins because they facilitate the transport of water and small neutral solutions, including glycerol and urea, across biological membranes. AKP-3 are localized in the basal or suprabasal layer of the epidermis, produced by all living epidermal layers - from the basal to granular - and disappear in the stratum corneum. Their spatial distribution corresponds to the water content; The basal and suprabasal living layers contain 75% water, while the stratum corneum contains only 10-15% water. The acidity of the skin behaves in the same way: being about 5 on the surface, it rises to 7 under the stratum corneum. Therefore, pH-sensitive ACP-3 is inhibited by acidic pH, which also increases the impermeability of the epidermal barrier.

As a result of research

To date, the mechanism of water transport by aquaporins is poorly understood. It is believed that the work of skin aquaporins affects the hydration and elasticity parameters of the organ. Thus, with aquaporin-3 deficiency in mice, skin hydration and elasticity decrease and the restoration of the skin barrier slows down. And when glycerol was added in this experiment, the condition of the skin improved.

In patients suffering from eczema, AKP-3 deficiency was identified in areas of skin with intercellular edema, confirming a possible relationship between the fluid movement defect, AKP-3 deficiency and epidermal edema. Deposition of AKP-3 in the epidermis of skin affected by atopic dermatitis is associated with fluid loss and dry skin. One study found an increase in AKP-3 when exposed to osmotic stress, namely high concentrations of NaCl, sorbitol, mannitol, sucrose and glucose. AKP-3 also accumulated in the epidermis of human skin after barrier damage caused by a series of treatments with adhesive tape or lipid removal with a 1:1 solvent mixture of ether and acetone.

Also, a significant decrease in AKP-3 in the facial epidermis was detected in women exposed to regular sun exposure compared to areas of skin protected from the sun. Interestingly, the decrease associated with insolation was detected only in women over 40 years of age, that is, the detected deficiency of aquaporin-3 during chronic sun exposure depended on age. These results indicate that AKP-3 synthesis is severely damaged with age and chronic sun exposure, and osmotic imbalance may occur in the epidermis with the development of dryness. A recent study found a decrease in AKP-3 levels with increasing age in both skin and cultured keratinocytes. In fibroblasts, the level of AKP-3 was significantly reduced in the group over 60 years of age compared with those aged 30-45 years (P < 0.05) and those under 20 years of age (P < 0.05). The authors of this study concluded that AKP-3 may be involved in the process of not only photoaging, but also chronobiological aging of the skin.

Proven Impact

The abundance and variability of aquaporins in human skin cells suggests that these channels may play an important role in skin physiology. ACPs may be key target proteins for enhancing resistance and improving skin surface quality, improving aging skin and photodamaged dryness. Currently, only an extract from the herb Ajuga turkestanica, a plant from Central Asia, has demonstrated an effect on the regulation of AKP-3.

In an experiment, a hydroalcoholic extract (70/30 v/v) of Ajuga turkestanica increased the expression of AKP-3 in the human epidermis after 17 days of application. Moreover, half sections of treated epidermis showed an increase in epidermal proliferation and differentiation over time of treatment. According to electron microscopy, the stratum corneum has become highly compact, noticeably thicker and more clearly differentiated. Electron micrographs also showed clearer differentiation of desmosomes, a thickened horny envelope, thinned corneocytes with narrow intercellular space, more numerous corneodesmosomes, and a well-oriented keratin network connected to desmosomal structures.

Then Ajuga turkestanica extract (0.3% w/w) was added to the oil-in-water emulsion complex and applied 2 times a day for 21 days to the skin of the forearm of 15 female volunteers aged 22-56 years. The researchers found a significant decrease in TEWL from days 7 to 21 in the treatment areas compared to the control area, indicating that the treatment improved epidermal barrier repair. This result indicates that formulations containing the active extract of Ajuga turkestanica, which increases the expression of AKP-3 and improves the differentiation of human epidermal keratinocytes, will improve barrier structures and repair human skin. Ajuga turkestanica is included today in formulations as an ingredient in highly effective cosmetics.

Prospects for application and study

The emergence of a new synthetic peptide capable of activating the synthesis of proteins of the aquaporin family is interesting. This invention relates to cosmetics, nutraceuticals or pharmaceutical compositions containing the claimed peptide formula as an active ingredient. The invention can also be used as a new active ingredient in cosmetics or nutraceuticals to improve the hydration and barrier function of the epidermis, stimulate skin regeneration, as well as as a new active ingredient in pharmaceuticals or pharmaceuticals, especially dermatological ones, to regulate and/or stimulate the activity of aquaporins and treat pathological dry skin and mucous membranes.

Water homeostasis of the epidermis is important for the appearance and physical abilities of the skin as well as for the water balance of the body. This depends on many factors, the quality of the barrier, water absorption by the epidermis, the content of water-retaining humectants, and external humidity. Water transport through aquaporins and aquaglyceroporins and glycerol transport through aquaglyceroporins are important for skin hydration. Aquaporins have been shown to be key proteins in improving skin resistance, texture and quality. In dermatoses accompanied by increased TEWL and reduced hydration of the stratum corneum, the expression of AKP-3 is damaged.

Recent studies have shown that AKP-3 expression is severely impaired with age and chronic sun exposure, and a defect in osmotic balance may lead to dry skin found in older patients and in areas exposed to excessive sun exposure.

Thus, the pharmacological and cosmetic use of aquaporins and their synthesis stimulators is promising for the treatment of skin conditions caused by excessive or decreased hydration. The above experimental results showed that the absence of aquaporins leads to intercellular edema. This demonstrates the drainage potential of topical aquaporins and their stimulators, the possibility of preventing the accumulation of water in the epidermis, and the possibility of using them in the treatment of dyshidrotic conditions.

Unfortunately, there is no data on the presence of an aquaporin network in the hypodermis, since such an action could be invaluable in the fight against cellulite. At the same time, an excess of aquaporins with an ineffective epidermal barrier can cause skin xerosis. Theoretically, in this case, a reverse reaction is possible - dry skin when using topical aquaporins or their stimulants. The possibility of correcting aquaporin deficiency states with glycerol, demonstrated in experiments on mice, is also interesting. All these data indicate that skin rehydration is a multifactorial process that requires further study and accumulation of practical experience.

Bibliography:

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[3] Papadopoulos, M. C., & Verkman, A. (2012). Aquaporin 4 and neuromyelitis optica. The Lancet Neurology, 11(6), 535–544. https://doi.org/10.1016/s1474-4422(12)70133-3