Роль структурных белков кожи в развитии атопического дерматита

Кандрашкина Ю.А., Орлова Е.А. Роль структурных белков кожи в развитии атопического дерматита. Consilium Medicum. 2025;27(6):361–365. DOI: 10.26442/20751753.2025.6.203306

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Kandrashkina JuA, Orlova EA. The role of structural skin proteins in the development of atopic dermatitis: A review. Consilium Medicum. 2025;27(6):361–365. DOI: 10.26442/20751753.2025.6.203306

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Аннотация

Атопический дерматит (АтД) – хроническое воспалительное заболевание кожи, существенно снижающее качество жизни. В патогенезе АтД основополагающими факторами являются дисфункция эпидермального барьера и нарушение иммунной регуляции. Кератиноциты выполняют барьерную функцию на физическом и химическом уровне. В процессе формирования рогового слоя происходит последовательная выработка белковых компонентов. Такие белки, как филаггрин, филаггрин 2, инволюкрин и лорикрин, имеют решающее значение для функционирования эпидермального барьера. Помимо дисфункции эпидермального барьера АтД характеризуется развитием кожного воспалительного процесса, вызванного Т-хелперами (Тh) 2-го типа. Цитокины, полученные из Тh-2, такие как интерлейкин (ИЛ)-4, 13 и 31, играют значимую роль в развитии и прогрессировании АтД. Среда, образованная цитокинами, продуцированными Th-2 и 22, при АтД мешает скоординированной эпидермальной дифференцировке и созреванию кератиноцитов, усугубляя продукцию структурных белков кожи, ухудшая при этом дисфункцию кожного барьера. Дисфункция кожного барьера играет важную роль в развитии АтД. При АтД снижается экспрессия структурных белков кожи, таких как филаггрин, инволюкрин, лорикрин. В настоящее время механизмы, посредством которых регулируется продукция структурных белков кожи, до конца не изучены, что открывает возможности для дополнительных исследований. Углубленное изучение данной проблемы несет перспективу для разработки новых стратегий в лечении АтД.

Ключевые слова: атопический дерматит, филаггрин, инволюкрин, лорикрин, интерлейкин

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Atopic dermatitis (AtD) is a chronic inflammatory skin disease that significantly reduces the quality of life. The underlying factors in the pathogenesis of AtD are dysfunction of the epidermal barrier and impaired immune regulation. Keratinocytes perform a barrier function at the physical and chemical levels. During the formation of the stratum corneum, protein components are sequentially produced. Proteins such as filaggrin, filaggrin 2, involucrin, and loricrin are critical for the functioning of the epidermal barrier. In addition to dysfunction of the epidermal barrier, AtD is characterized by the development of a skin inflammatory process caused by T-helpers (Th) type 2. Th-2-derived cytokines, such as interleukin (IL)-4, 13 and 31, play a significant role in the development and progression of AtD. The environment formed by Th-2 and Th-22-derived cytokines in AtD interferes with coordinated epidermal differentiation and maturation of keratinocytes, aggravating the production of structural skin proteins, thereby worsening the dysfunction of the skin barrier. Dysfunction of the skin barrier plays an important role in the development of AtD. In AtD, the expression of structural skin proteins such as filaggrin, involucrin, and loricrin decreases. To date, the mechanisms by which the production of structural skin proteins is regulated have not been fully studied, which opens up opportunities for additional research. In-depth study of this problem holds promise for the development of new strategies in the treatment of AtD.

Keywords: atopic dermatitis, filaggrin, involucrin, loricrin, interleukin

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3. Wollenberg A, Barbarot S, Bieber T, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J Eur Acad Dermatol Venereol. 2018;32(5):657-82. DOI:10.1111/jdv.14891
4. Schoch JJ, Anderson KR, Jones AE, et al. Atopic Dermatitis: Update on Skin-Directed Management: Clinical Report. Pediatrics. 2025;e2025071812. DOI:10.1542/peds.2025-071812
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6. Wong R, Geyer S, Weninger W, et al. The dynamic anatomy and patterning of skin. Exp Dermatol. 2016; 25:92-8. DOI:10.1111/exd.12832
7. Jensen JM, Proksch E. The skin's barrier. G Ital Dermatol Venereol. 2009;144:689-700.
8. Szondi DC, Crompton RA, Oon L, et al. A role for arginase in skin epithelial differentiation and antimicrobial peptide production. British Journal of Dermatology. Br J Dermatol. 2025; 00:1-11. DOI:10.1093/bjd/ljaf057
9. Murashkin NN, Savelova AA, Ivanov RA et al. Modern concepts of the role of the epidermal barrier in the development of the atopic phenotype in children. Voprosy sovremennoi pediatrii. 2019;18(5):386-92 (in Russian). DOI:10.15690/vsp.v18i5.2064
10. Zhao LP, Di Z, Zhang L, et al. Association of SPINK5 gene polymorphisms with atopic dermatitis in Northeast China. J Eur Acad Dermatol Venereol. 2012;26(5):572-5DOI:10.1111/j.1468- 3083.2011.04120.x
11. Furue M. Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis. Int J Mol Sci. 2020;21(15):5382. DOI:10.3390/ijms21155382
12. Jang SI, Steinert PM. Loricrin expression in cultured human keratinocytes is controlled by a complex interplay between transcription factors of the Sp1, CREB, AP1, and AP2 families. J Biol Chem. 2002;277(44):42268-79. DOI:10.1074/jbc.M205593200
13. Beilin AK, Rippa AL, Sharobaro VI, et al. The Reconstructed Human Epidermis in vitro – a Model for Basic and Applied Research of Human Skin. Vestnik dermatologii i venerologii. 2020;96(2):24-34 (in Russian). DOI:10.25208/vdv1107
14. Bikle DD. Vitamin D and the skin: Physiology and pathophysiology. Rev Endocr Metab Disord. 2012;13(1):3-19. DOI:10.1007/s11154-011-9194-0
15. Abhishek S, Palamadai Krishnan S. Epidermal Differentiation Complex: A Review on Its Epigenetic Regulation and Potential Drug Targets. Cell J. 2016;18(1):1-6. DOI:10.22074/cellj.2016.3980
16. Cho YH, Kim JW, Kim N, et al. Lactobacillus brevis-Derived Exosomes Enhance Skin Barrier Integrity by Upregulating Key Barrier-Related Proteins. Clin Cosmet Ivestig Dermatol. 2025;18:1151-62. DOI:10.2147/CCID.S512793
17. Ferrara F, Yan X, Pecorelli A, et al. Combined exposure to UV and PM affect skin oxinflammatory responses and it is prevented by antioxidant mix topical application: Evidences from clinical study. J Cosmet Dermatol. 2024;23(8):2644-56. DOI:10.1111/jocd.16321
18. Drislane C, Irvine AD. The role of filaggrin in atopic dermatitis and allergic disease. Ann Allergy Asthma Immunol. 2020;124(1):36-43. DOI:10.1016/j.anai.2019.10.008
19. Stefanovic N, Irvine AD. Filaggrin and beyond: New insights into the skin barrier in atopic dermatitis and allergic diseases, from genetics to therapeutic perspectives. Ann Allergy Asthma Immunol. 2024;132(2):187-95. DOI:10.1016/j.anai.2023.09.009
20. Kalankariyan S, Thottapillil A, Saxena A, et al. An in silico approach deciphering the commensal dynamics in the cutaneous milieu. NPJ Syst Biol Applications. 2025;11(1):42. DOI:10.1038/s41540-025-00524-y
21. Barthe M, Clerbaux LA, Thénot JP, et al. Systematic characterization of the barrier function of diverse ex vivo models of damaged human skin. Front Med. 2024;11:1481645. DOI:10.3389/fmed.2024.1481645
22. Seguchi T, Cui CY, Kusuda S, et al. Decreased expression of filaggrin in atopic skin. Arch Dermatol Res. 1996;288:442-6.
23. Bak SG, Lim HJ, Won YS, et al. Regulatory effects of Ishige okamurae extract and Diphlorethohydroxycarmalol on skin barrier function. Heliyon. 2024;10(23):e40227. DOI:10.1016/j.heliyon.2024.e40227
24. Tamrazova OB, Glukhova EA. Unique molecule filaggrin in epidermal structure and its role in the xerosis development and atopic dermatitis pathogenesis. Russian Journal of Clinical Dermatology and Venereology. 2021;20(6):102-10 (in Russian). DOI:10.17116/klinderma202120061102
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26. Shamilov R, Robinson VL, Aneskievich BJ. Seeing Keratinocyte Proteins through the Looking Glass of Intrinsic Disorder. Int J Mol Sci. 2021;22(15):7912. DOI:10.3390/ijms22157912
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Авторы

Ю.А. Кандрашкина*¹, Е.А. Орлова²

¹ФГБОУ ВО «Пензенский государственный университет», Пенза, Россия;
²Пензенский институт усовершенствования врачей – филиал ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Пенза, Россия
*novikova10l@mail.ru

________________________________________________

Julia A. Kandrashkina*¹, Ekaterina A. Orlova²

¹Penza State University, Penza, Russia;
²Penza Institute for Advanced Medical Studies – branch of the Russian Medical Academy of Continuous Professional Education, Penza, Russia
*novikova10l@mail.ru

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