E.L. Iskra, A.S. Iskra, V.O. Polyakova, R.A. Nasirov Saint-Petersburg State Pediatric Medical University, Litovskay street, 2, Saint-Petersburg, 194100, Russian Federation E-mail: [email protected]

Atopic dermatitis (AD) is characterized by a violation of the epidermal barrier dysfunction. This review examines the work of the authors who describe mutations in the filaggrin gene as predisposing factors for the development of AD and describe the dysfunction of the epidermal barrier as a causal mechanism. In recent years, signaling molecules have been widely studied as a key factor in the development of a particular pathology, including signaling molecules of intercellular contacts that play an important role in the pathogenesis of AD. Claudins are the main proteins that make up dense compounds. The analyzed articles in which proteins with dense compounds of claudin-1,7, claudin-10, occludin. It determines the density of these contacts and plays an important role in providing the barrier function. Evaluation of the expression level for further correction of proteins with dense compounds may be an important therapeutic target for targeted therapy of various diseases, including AD.
transmembrane protein, atopic dermatitis, claudin, dense compound, occludin

Список литературы: 
  1. Weidinger S., Novak N. Atopic dermatitis. Lancet. 2016. 12; 387:1109-1122.
  2. David Boothe W., Tarbox J.A., Tarbox M.B. Atopic Dermatitis: Pathophysiology. Adv Exp Med Biol. 2017; 1027: 21–37.
  3. Kubo A., Nagao K., Amagai M. Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases. J. Clin. Invest. 2012; 122: 440–7.
  4. Guttman-Yassky E., Waldman A., Ahluwalia J., Ong P.Y., Eichenfield L.F. Atopic dermatitis: pathogenesis. Semin Cutan Med Surg. 2017; 36: 100–3. https://10.12788/j.sder.2017.036.
  5. Milatz S., Breiderhoff T. One gene, two paracellular ion channels-claudin-10 in the kidney. Pflugers Arch. 2017; 469: 115–21.
  6. Trubitt R.T., Rabeneck D.B., Bujak J.K., Bossus M.C., Madsen S.S., Tipsmark C.K. Transepithelial resistance and claudin expression in trout RTgill-W1 cell line: effects of osmoregulatory hormones. Comp Biochem Physiol A Mol. Integr Physiol. 2015; 182: 45–52.
  7. Milatz S. New claudinopathy based on Claudin-10 mutations. Int J. Mol Sci. 2019; 20: 5396. /ijms20215396.
  8. Olinger E., Houillier P., Devuyst O. Claudins: a tale of interactions in the thick ascending limb. Kidney Int. 2018; 93: 535–7.
  9. Volksdorf T., Heilmann J., Eming S.A., Schawjinski K., Zorn-Kruppa M., Ueck C., Vidal-Y-Sy S., Windhorst S., Jücker M., Moll I., Brandner J.M. Tight Junction Proteins Claudin-1 and Occludin Are Important for Cutaneous Wound Healing. Am. J. Pathol. 2017; 187: 1301–12.
  10. Bhat A.A., Syed N., Therachiyil L., Nisar S., Hashem S., Macha M.A., Yadav S.K., Krishnankutty R., Muralitharan S., Al-Naemi H., Bagga P., Reddy R., Dhawan P., Akobeng A., Uddin S., Frenneaux M.P., El-Rifai W., Haris M. Claudin-1, A Double-Edged Sword in Cancer. Int J. Mol Sci. 2020; 21: 569.
  11. Ouban A. Claudin-1 role in colon cancer: An update and a review. Histol Histopathol. 2018; 33: 1013–9.
  12. Gonzalez-Mariscal L., Namorado Mdel C., Martin D., Sierra G., Reyes J.L. The tight junction proteins claudin-7 and – 8 display a different subcellular localization at Henle’s loops and collecting ducts of rabbit kidney. Nephrol Dial Transplant. 2006; 21: 2391–8.
  13. Clarke T.B., Francella N., Huegel A., Weiser J.N. Invasive bacterial pathogens exploit TLR-mediated downregulation of tight junction components to facilitate translocation across the epithelium. Cell Host Microbe. 2011; 9: 404–14.
  14. Curry J.N., Tokuda S., McAnulty P., Yu A.S.L. Combinatorial expression of claudins in the proximal renal tubule and its functional consequences. Am J Physiol Renal Physiol. 2020; 318: 1138–46.
  15. Inai T., Sengoku A., Guan X., Hirose E., Iida H., Shibata Y. Heterogeneity in expression and subcellular localization of tight junction proteins, claudin-10 and -15, examined by RT-PCR and immunofluorescence microscopy. Arch Histol Cytol. 2005; 68: 349–60.
  16. Inai T., Kamimura T., Hirose E., Iida H., Shibata Y. The protoplasmic or exoplasmic face association of tight junction particles cannot predict paracellular permeability or heterotypic claudin compatibility. Eur J. Cell Biol. 2010; 89: 547–56.
  17. Furuse M., Hirase T., Itoh M., Nagafuchi A., Yonemura S., Tsukita S., Tsukita S. Occludin: a novel integral membrane protein localizing at tight junctions. J. Cell Biol. 1993; 123: 1777–88.
  18. Ando-Akatsuka Y., Saitou M., Hirase T., Kishi M., Sakakibara A., Itoh M., Yonemura S., Furuse M., Tsukita S. Interspecies diversity of the occludin sequence: cDNA cloning of human, mouse, dog, and rat-kangaroo homologues. J. Cell Biol. 1996; 133: 43–7.
  19. Feldman G.J., Mullin J.M., Ryan M.P. Occludin: structure, function and regulation. Adv Drug Deliv Rev. 2005; 57: 883–917.
  20. Richter J.F., Hildner M., Schmauder R., Turner J.R., Schumann M., Reiche J. Occludin knockdown is not sufficient to induce transepithelial macromolecule passage. Tissue Barriers. 2019; 7: 1612661.
  21. Eilken H.M., Diéguez-Hurtado R., Schmidt I., Nakayama M., Jeong H.W., Arf H., Adams S., Ferrara N., Adams R.H. Pericytes regulate VEGF-induced endothelial sprouting through VEGFR1. Nat Commun. 2017; 8: 1574.
  22. Brigidi G.S., Bamji S.X. Cadherin-catenin adhesion complexes at the synapse. Curr Opin Neurobiol. 2011; 21: 208–14.
  23. Senger D.R., Galli S.J., Dvorak A.M., Perruzzi C.A., Harvey V.S., Dvorak H.F. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983; 219: 983–5.
  24. Onder T.T., Gupta P.B., Mani S.A., Yang J., Lander E.S., Weinberg R.A. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 2008; 68: 3645–54.
  25. van Roy F. Beyond E-cadherin: roles of other cadherin superfamily members in cancer. Nat Rev Cancer. 2014; 14: 121–34.
  26. Barratt S.L., Flower V.A., Pauling J.D., Millar A.B. VEGF (Vascular Endothelial Growth Factor) and Fibrotic Lung Disease. Int J. Mol Sci. 2018; 19: 1269.
  27. Hoeben A., Landuyt B., Highley M.S., Wildiers H., Van Oosterom A.T., De Bruijn E.A. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004; 56: 549–80.
  28. Veeravagu A., Hsu A.R., Cai W., Hou L.C., Tse V.C., Chen X. Vascular endothelial growth factor and vascular endothelial growth factor receptor inhibitors as anti-angiogenic agents in cancer therapy. Recent Pat Anticancer Drug Discov. 2007; 2: 59–71.
  29. Apte R.S., Chen D.S., Ferrara N. VEGF in Signaling and Disease: Beyond Discovery and Development. Cell. 2019; 176: 1248–64.
  30. Melincovici C.S., Boşca A.B., Şuşman S., Mărginean M., Mihu C., Istrate M., Moldovan I.M., Roman A.L., Mihu C.M. Vascular endothelial growth factor (VEGF) – key factor in normal and pathological angiogenesis. Rom J. Morphol Embryol. 2018; 59: 455–67.
  31. Guttman-Yassky E., Waldman A., Ahluwalia J., Ong P.Y., Eichenfield L.F. Atopic dermatitis: pathogenesis. Semin Cutan Med Surg. 2017; 36: 100–3.