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Research Progress on Percolation Barrier of Epidermis and other Barrier Functions


The skin is located in the outermost layer of human body surface, in addition to absorption, secretion, excretion, metabolism, immunity, body temperature regulation and sensory other physiological functions, but also has a barrier function.The broad sense of skin barrier function includes skin physical barrier, osmotic barrier, pigment barrier, nerve barrier, immune barrier and other functions.Epidermal permeability barrier can prevent external chemical, physical, mechanical and biological factors of skin damage, and to prevent loss of water, inorganic salt and other nutrients through skin, and other skin barrier function, such as acidic barrier, micro ecological barrier, such as immune barrier has the close relationship between, jointly maintain the normal physiological metabolism of the skin.The research progress of epidermal permeable barrier and other barrier functions is summarized as follows:

1.Epidermal permeability barrier function

The epidermal permeable barrier is a bridge connecting the body with the external environment. It is mainly composed of the cuticle layer, that is, a laminated plate layer formed in the continuous hydrophobic intercellular lipids formed by the layer of keratinocytes disappearing from 5-15 layers of nuclei and organelles.Professor Peter Eli – 70 s, as the image of the characteristics of the structure compared to “brick wall structure”, among them, the cutin cell is “bricks”, from basal layer to layer formed by cutin cell migration process of proliferation and differentiation, intercellular lipid composition “mortar”, mainly in the epidermal granular layer plate small body to synthesize, and in the form of a cell to spit release in the cutin cell by amide (ceramide, Cer) (50%), free fatty acid (10% ~ 20%), cholesterol (25%).At the same time, by the intermediate filament protein aggregation armour (filaggrin, FLG) and protein (loricrin, LOR), within the outer protein (such as involucrin, INV) formed in the cutin cell membrane is widely crosslinking to form the Angle of the mantle, and the intercellular lipid mutual crisscross, can resist protease digestion, acid and alkali stimulation and stimulation, improve the stability of epidermal permeability barrier.Therefore, the keratinocytes are embedded in the cutin layer structure formed by interstitium, which plays an important role in maintaining the skin barrier function.

Maintaining good skin barrier function and preventing water loss is an important function of cuticle and plays an important role in skin health.Under normal circumstances, the cuticle layer through the epidermal moisture loss is 2 ~ 5g/h·cm2. When the cuticle is damaged, the transepidermalwater loss (TEWL) will increase. If the whole cuticle layer is stripped, the moisture through the skin infiltration can increase by 30 times.When external humidity drops below zero, water evaporates from the skin surface until the cuticle surface reaches a new balance with the surrounding environment.When the temperature decreases, the cuticle moisture content also decreases, so the skin tends to crack in cold and dry weather.If the cell membrane is damaged (friction, excessive use of stain remover or lipid solvent), water can be lost from the cell even in good ambient humidity.In addition, due to the weakening of skin barrier function, the moisture diffusion in the skin lesions is accelerated, the skin becomes drier, and a series of inflammatory and immune responses are triggered, which will aggravate the occurrence of various skin diseases, such as psoriasis, eczema and atopic dermatitis.

Epidermal permeable barrier is closely related to other skin barrier functions.When the epidermal permeable barrier is damaged, it can cause problems such as abnormal skin immunity and microbial infection. Meanwhile, when other skin barrier functions are abnormal, it can further aggravate the damage of the epidermal permeable barrier function.


2.Epidermal acid barrier and epidermal permeable barrier

Nearly a century ago, Schade first coined the term “acid-coat” to describe the inherent acidity of the cuticle, causing more scientists to focus on the importance of changes in pH on the skin’s surface.Research in the past decade has shown that the pH value of skin surface can affect the stability of epidermal permeable barrier, the integrity and cohesion of cuticle layer and the anti-bacterial defense mechanism of skin.Normal skin tends to be acidic, with a pH of 5.5 ~ 7.0 and a minimum of 4.0. Only when the skin is within the normal pH range, that is, when it is slightly acidic, can the skin reach the optimal state in resisting external erosion.

Recent studies have shown that pH changes on the skin surface are also important for maintaining normal epidermal permeability barrier function.Maum et al. used acetone and adhesive tape to destroy the epidermal barrier in hairless mice.Stenzaly et al. showed that when the phospholipase A2 or sodium ion exchanger involved in cuticle acidification was blocked or knocked out, the stability of epidermal osmotic barrier and the integrity of cuticle could be destroyed.Hachem et al. used a hairless mouse model and found that when skin surface pH dropped, the epidermal osmotic barrier could be restored even if there was no change in the epidermal basal layer.

The reason why pH value of skin surface affects the function of epidermal permeable barrier may be related to the fact that many key enzymes in the lipid composition synthesis process of epidermal permeable barrier are ph-dependent enzymes.For example, the two key enzymes involved in the synthesis of ceramides, the major component of lipids between cells in the stratum corneum, are the acidic phospholipase and the caspase, which require a pH of 4.5 and 5.6, respectively.Experiments showed that the activity of the ace-glucosidase decreased 10 times from 5.5 to 7.4.In addition, the formation of lipid secreted by lamellar bodies and the lamellar structure of the cuticle requires an acidic environment.

As the acid environment can promote the repair of epidermal permeable barrier, some scholars have used acidic substances in the treatment of skin diseases related to the damage of epidermal permeable barrier and achieved good curative effect.Hachem et al. found that polyhydroxy acids could improve epidermal permeability barrier function in neonates and the elderly.According to studies conducted by Chinese scholars like lai wei, the pH value of skin lesions in patients with atopic dermatitis was significantly higher than that of normal skin, and the buffer capacity of acid/alkali was decreased. After applying 5% l-lactic acid gel on the surface of skin lesions, the pH value of skin lesions was decreased. Meanwhile, the TEWL value was lower than that in unused parts, and the skin moisture content was increased.Therefore, it can be further explained that the epidermal osmotic barrier can be repaired with external acidic substances to achieve the purpose of treating some skin diseases.

3.Epidermal permeable barrier and skin immune and inflammatory response

The epidermal permeable barrier also regulates the skin’s immune response.In order to verify the epidermal permeability barrier after damage to the skin effect on immune response, Godefroy tape adhesion of consecutive methods, such as destruction of BALB/c mice epidermal permeability barrier, and daub on the skin of mice containing diphtheria toxin non-toxic variants (CRM197) and cholera virus antigen, and in 21 d and 42 d again daub, to strengthen the immune response.It was found that the immune response of antigens was detected in mice with damaged epidermal osmotic barrier, but not in normal mice.The results indicated that a variety of foreign antigens can invade the human body through the damaged epidermal osmotic barrier and produce immune and inflammatory responses.Pan et al. found that free fatty acids, fatty acid binding protein 4 and fatty acid binding protein 5 in the extracellular matrix play an important role in maintaining the normal physiological function of memory T lymphocytes.Serine palmitine transferase is a key enzyme in the synthesis of neuramide in the intercellular lipid of the cuticle. Nakajima et al. used mice that knocked out the serine palmitine transferase to observe the changes of skin immune response when the synthesis of neuramide decreased.Two weeks later, it was found that langerhans cells were more active, and their ability to migrate to the lymph nodes was also increased. At the same time, the amount of T lymphocytes was increased, excessive keratinization, acanthic processes, loss of granular layer and infiltration of inflammatory cells appeared in the skin, presenting psori-like skin lesions.It is indicated that the intercellular lipid components that form the epidermal osmotic barrier “mortar” play an important role in inducing the skin immune response.

In turn, skin inflammation and immune response can affect epidermal permeability barrier function.The expression of il-22 in skin lesions of atopic dermatitis patients was significantly increased. Lou et al. found that il-2 could not only induce the immune response with Th2 as the main characteristic, but also cause the damage of epidermal permeability barrier by activating GRP signaling pathway through a special induction transgenic skin model.

4.Epidermal permeable barrier and epidermal microecology

Skin is the first barrier for human body to resist the invasion and growth of pathogenic bacteria. There are many microorganisms on the skin, some of which, due to long-term mutual adaptation, can live on human skin for a long time.These microorganisms, which are closely related and interact with the host, constitute the skin microecology.Therefore, epidermal osmosis barrier and microecology also constitute the integration of interaction, and changes of either side can lead to the occurrence of diseases.

Van Drongelen et al. showed that after silencing the main component of the silk polymerin in the upper keratinocytes of the cutin layer, the colonization of the epidermis of staphylococcus aureus significantly increased, and the expression of il-8 induced by staphylococcus aureus also increased, resulting in inflammatory reaction and infection in the skin.Jinnest et al. compared the correlation between changes of epidermal penetration barrier and bacterial colonization in 30 adult patients with atopic dermatitis, and found that those patients with atopic dermatitis who had positive expressions of staphylococcus aureus, malassezia and candida had increased water loss through the epidermis compared with those who had negative expressions of these bacteria and fungi.Therefore, when the epidermal permeation barrier is damaged, it will promote the colonization of bacteria in the skin. A large number of microbial colonization can promote the invasion of microbial antigens into the skin through the damaged epidermal permeation barrier, thus leading to the occurrence of ige-related allergic reactions.

At the same time, the skin as the body to resist the invasion of pathogenic bacteria and growth of the first barrier, in terms of defense microbes, in addition to epidermal permeability barrier, partial acid environment, has also benefited from the body’s natural defense mechanisms, namely the antibacterial peptides, antibacterial peptides are abundant on the on the skin of small peptide, mainly in the skin deep, and to the corneous layer, in the first line of defense against potential pathogens plays a vital role.The antibacterial peptides found in human body are mainly defensins and cathelicidins.Aberg et al. found that after 1h of disruption of epidermal permeability barrier function, the expression of epidermal antimicrobial polypeptide protein and its mRNA was significantly enhanced, and the expression of catheli-cidin (ll-37)mRNA and calcu-defensin was also increased.Clausen, experiments have confirmed that the skin micro ecology and the relationship between the permeability barrier, by detecting 25 atopic dermatitis patients and in skin lesions and 11 healthy controls in skin lesions in the stratum corneum beta defense, TEWL and lesion score, found her lesions area beta defense element is significantly higher than the skin area and the healthy controls, and TEWL and lesion score is higher also.Czarnowicki et al. applied vaseline on the skin surface of patients with atopic dermatitis and found increased expression of filaggrin and bioluminin, as well as increased expression of antimicrobial peptides.All these studies have shown that damage of epidermal permeable barrier can affect skin microecological balance and play an important role in skin biological defense.


To sum up, epidermal osmotic barrier function plays an important role in regulating various biological functions of skin, and constitutes an integral defense system together with other skin barrier functions, such as immune barrier, acidic barrier and micro-ecology.When one function changes, other functions are affected, leading to skin diseases.Therefore, the clinical treatment of skin diseases not only needs anti-immune and anti-inflammatory treatment, but also needs to pay attention to repairing the damaged skin barrier, adjusting the acidic environment of skin surface and maintaining the homeostasis of micro-ecology.For example, studies have confirmed that TEWL in atopic dermatitis is elevated, and there are inflammatory reactions and bacterial colonization, suggesting that the disease not only has damaged epidermal permeability barrier, but also has damaged immune barrier and microecological barrier. Therefore, clinical treatment of the disease requires not only anti-inflammatory treatment, but also repair epidermal permeability barrier and antibacterial treatment.

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