In recent years, a large number of studies at home and abroad have shown that there is a close relationship between the epidermal permeability barrier and the pigment barrier. The epidermal pigment barrier can affect the epidermal permeability barrier function through the acidic environment of the epidermis and the pigment precursor material; while the epidermal permeability barrier regulates the epidermal pigment barrier function through lipid components and substances secreted by keratinocytes. Under normal circumstances, these two barrier functions should be in a steady state, and in some pigmented diseases (such as chloasma, vitiligo, etc.), the function of the two is abnormally changed. This paper will study the correlation between the two. The progress is reviewed.
1.Epidermal permeability barrier
The stratum corneum is the main structure that maintains the barrier function of the epidermal permeability. It usually consists of 10 to 25 layers of keratinocytes and intercellular lipids. In 1983, Professor Peter proposed the “brick wall structure” theory, pointing out that keratinocytes are “bricks”, the lipid component filled in the keratinocyte space is “mortar”, and the lipid components mainly include ceramide, cholesterol, free fatty acids. They are mixed in an appropriate ratio (50% ceramide, 25% cholesterol and 15% free fatty acid) to form the main structure of the epidermal permeability barrier, the stratified lamellar structure. This “brick wall structure” plays a powerful barrier function to protect the body from harmful irritations such as physical, chemical, and microbial diseases. It can also effectively prevent excessive loss of water and nutrients. Transepidermal water loss (TEWL) is an important indicator for evaluating the barrier function of epidermal permeability. The epidermal permeability barrier function is affected by various factors such as epidermal pH, ions, lipids, and keratinocyte differentiation.
2. Epidermal pigment barrier
The basal layer of melanocytes and the melanin produced by them maintain the epidermal pigment barrier function and prevent the body from being damaged by excessive ultraviolet radiation. Melanocytes transfer melanin-rich melanin bodies to the surrounding keratinocytes and redistribute them around the nucleus. Melanin protects by absorbing and scattering ultraviolet rays. The strength of this protection is mainly related to the melanin content, type, and volume and distribution of melanin in keratinocytes. Depending on the synthetic route and the raw materials, melanin bodies can synthesize brown-black melanin and red-yellow brown melanin. Del et al found that regardless of the depth of skin color, the pigment of human epidermis consists of approximately 74% of melanin and 26% of melanin; however, people with lighter skin have less photoreceptor content of melanin, so they are more UV-sensitive. sensitive. Abnormalities in any part of melanin metabolism may lead to pigmented diseases.
3. Relationship between epidermal permeability barrier and pigment barrier
3.1 Effect of pigment on epidermal permeability barrier function
Professor Peter et al. proposed a hypothesis based on the evolutionary history of human beings and the evolution of skin color. It is believed that human skin initially produces pigments to enhance the epidermal barrier function, especially the permeability barrier function. To adapt to the strong environment of dry and ultraviolet radiation. People of different skin types have different resistance to ultraviolet rays due to differences in epidermal melanin, and the barrier function of epidermal permeability is also different. Research by Gunathilake et al. found that people with darker skin after breaking the epidermal permeability barrier with tape have a faster recovery rate than those with lighter skin, and this difference is not related to race, but only related to skin pigment type (ie, skin tone), indicating health. People with deeper skin than those with lighter skin are more powerful and less susceptible to damage. The reason may be related to the acidic environment of the epidermis. Melanin is an acidic lysosomal-associated organelle. The number of melanocytes of dark-skinned humans is large. When melanosomes follow keratinocytes. Differentiation is degraded or detached with keratinocyte replacement and can cause epidermal acidity. The acidic environment contributes to the recovery of the epidermal permeability barrier, which may be related to the strongest activity of the lipid synthesis-related enzymes in a suitable acidic environment. Yan Maoqiang and other experiments have also confirmed this phenomenon. When the tape breaks the skin permeability barrier, the melanin body of the granular layer can quickly secrete melanin particles to the junction of the granular layer and the stratum corneum, so that the stratum corneum quickly returns to the optimal pH state. The activity of β-glucocerebrosidase and acid sphingomyelinase is enhanced to promote lipid synthesis and formation of a lamellar structure. In addition, Kovacs et al. found that the intermediate product of melanogenesis, 5,6-dihydroxyindole-2-carboxylic acid (DHICA), may be a messenger between melanocytes and keratinocytes, which inhibits keratinocyte proliferation and increases Expression of early markers of keratinocytes (keratin K1, K10, involucrin) and late (gabbin and filaggrin) differentiation markers. These factors are closely related to the formation of the epidermal permeability barrier function. Therefore, a person with a deep complexion can regulate the acidic environment of the epidermis by its own melanosome degradation or shedding process or maintain the homeostasis of the epidermal permeability barrier function through the intermediate product DHICA of the melanin synthesis process. Epidermal permeability barrier function may be abnormally changed in different pigment abnormalities. For example, chloasma and vitiligo have a reduced permeability of the epidermal permeability barrier. The stratum corneum of the chloasma lesions became thinner and the rate of barrier repair was significantly delayed. The melanin in the chloasma lesions is mainly distributed in the deep layer of the epidermis, while the superficial content is less, which may lead to an increase in the melanin content of the chloasma lesions but not to promote the repair of the epidermal permeability barrier by affecting the pH of the stratum corneum. Liu et al found that there was no significant difference between the TEWL and the surrounding normal skin in the white spot area of vitiligo patients. However, after the barrier was destroyed by tape, the permeability barrier function of the white spot area was slower than that of normal skin. Patients with vitiligo-protected skin that are vitiligo should be more susceptible to UV damage and increase the risk of skin cancer, but vitiligo patients are even more resistant to UV rays and have a lower risk of developing skin cancer than normal people. The reason may be that the thickness of the epidermal layer (especially the stratum corneum) in the depigmentation area is significantly increased, which compensates for the destruction of the pigment barrier, thereby preventing excessive ultraviolet rays from penetrating the epidermis and causing damage. It can be seen that the absence or abnormal distribution of epidermal melanin has an effect on the barrier function of epidermal permeability.
3.2 Effect of epidermal permeability barrier on pigments
Epidermal lipids are the main component of the epidermal permeability barrier. Reduced lipid content, ratio and structural changes affect the barrier function of the epidermal permeability and are associated with a variety of skin diseases such as dry skin, atopic dermatitis, and psoriasis. In recent years, studies have shown that certain lipid components also affect melanin production. Ceramide is the most important component in the intercellular lipids of the stratum corneum, accounting for about half of the total lipid content of the epidermis, and has important physiological functions such as regulating cell proliferation, differentiation and apoptosis. Ceramide analogues have been added as moisturizers to skin care products because of their good moisturizing effect. In recent years, their whitening effects have gradually attracted people’s attention. Jeong et al. found that the synthetic ceramide analog PC102 degrades tyrosinase and regulates MITF to inhibit melanogenesis. Cholesterol is another important lipid component that forms a barrier to the epidermal permeability. It is mainly synthesized by granules and spinous keratinocytes and stored in lamellar bodies to promote melanin synthesis. In addition, Lee et al. found that reduction of cholesterol synthesis by down-regulating hydroxymethylglutaryl coenzyme A reductase gene expression inhibited melanogenesis. In addition to lipid components, there is evidence that keratinocytes, another important component of the epidermal permeability barrier, can also regulate melanin metabolism. Keratinocytes can affect melanogenesis by regulating the dose of ultraviolet light into the epidermis, which can reflect 5% to 10% of incident light on the skin surface, thereby reducing melanin production and transport. Keratinocytes, as a component of the “epidermal pigment unit”, play an important role in the production and transport of melanin. The basic fibroblast growth factor, NO, endothelin 1, nerve growth factor, PGE2 and proopiomelanosome-derived peptide released by keratinocytes can affect pigmentation by paracrine action. In addition, studies such as Lo have shown that keratinocytes can also regulate melanogenesis in melanocytes by releasing exosomes. Therefore, the state of the epidermal permeability barrier function has a certain influence on melanogenesis. The gene chip showed that the expression of multiple lipid metabolism-related genes was decreased in the lesions of the chloasma, and some genes related to the epidermal permeability barrier function also showed abnormal expression, suggesting that the pathogenesis of melasma may be related to lipid metabolism disorder and epidermis. The permeability barrier function is abnormal. In addition, Wang Yinjuan et al. performed immunohistochemistry on 10 cases of chloasma lesions and normal skin, and found that keratin (K6, K10, K14), keratinized envelope protein (capsule protein, filaggrin, involucrin) And the abnormal expression of acid ceramidase 1 suggests that the permeation barrier function of the chloasma is abnormal. When the patient’s epidermal permeability barrier function is impaired, the skin’s ability to resist UV rays is weakened, and it may be easier to activate melanocytes to produce melanin, which induces chloasma. Therefore, care should be taken to repair the skin barrier when treating chloasma. In recent years, studies have found that a variety of drugs for the treatment of pigmentation disorders, such as tranexamic acid, antioxidants, histamine, etc., can also affect the barrier function of the epidermal permeability. A large number of studies have reported that topical tranexamic acid or antioxidants are effective methods for treating chloasma. In recent years, they have been found to promote the repair of epidermal permeability barrier function; tranexamic acid may affect some keratinocyte differentiation. Expression of exfoliation-related proteins promotes skin barrier repair, while antioxidants can improve epidermal permeability by affecting differentiation of epidermal keratinocytes, synthesis of epidermal lipids, formation and secretion of lamellar bodies, and lamellar lamellar membrane maturation. Features. In addition, Huang Xiaofeng and others found that only the “Vaseline Moisturizing Dew” which has the function of moisturizing and repairing the skin barrier can significantly improve the pigmentation of chloasma. Histamine is an inflammatory mediator that has been shown to inhibit epidermal keratinocyte differentiation and impair the epidermal permeability barrier function in vitro. Liu et al treated with 1% histamine solution wet dressing for vitiligo, 2 times / d, 30 min / time, a total of 5 ~ 11 weeks, the melanin index of the white spot increased by 130% than before treatment, indicating that histamine can significantly promote pigmentation. However, the rate of epidermal permeability barrier recovery in the leukoplakia of topical histamine was faster than that in the stromal control group. The reason may be that the expression of histamine upregulated keratin envelope protein accelerates the permeability barrier repair, and may also be related to histamine-induced pigmentation. Promoting epidermal permeability barrier repair is associated with reduced hemorrhagic effects of histamine. In summary, restoring the homeostasis of the epidermal permeability barrier may help treat pigmented diseases such as chloasma and vitiligo.
As the structure of the body directly in contact with the outside world, the importance of the skin defense function is self-evident. The skin permeability barrier and the pigment barrier are two important barriers to protect the body, especially the defense against ultraviolet rays. Maintaining a balance between the two functions allows the skin’s defense function to be optimal to better protect against external environmental damage, while certain pigmented diseases (such as chloasma and vitiligo) have significant epidermal permeability barrier function. The damage may be related to the occurrence and development of the disease. Therefore, clinical use of the repair of the epidermal permeability barrier may help treat diseases such as chloasma and vitiligo, but its effects and specific mechanisms still need further study.