The Blood-Salivary Barrier as a Multifaceted System: a Review

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Published: May 28, 2026
DOI: https://doi.org/10.18097/BMCRM00307
Keywords:
BSB; salivary glands; oral mucosa; microbiome; immune system; intercellular connections

Main Article Content

E.I. Dyachenko
Biochemistry Research Laboratory, Omsk State Pedagogical University, 14 Tukhachevsky embankment str., Omsk, 644099, Russia
E.A. Sarf
Biochemistry Research Laboratory, Omsk State Pedagogical University, 14 Tukhachevsky embankment str., Omsk, 644099, Russia
L.V. Bel’skaya
Biochemistry Research Laboratory, Omsk State Pedagogical University, 14 Tukhachevsky embankment str., Omsk, 644099, Russia

Abstract

The purpose of this review is to provide a comprehensive description of the blood-salivary barrier and systematize the result of recent studies on its structure and function in healthy and diseased states. The blood-salivary barrier (BSB) is considered a multifaceted system, which includes following key components: the salivary glands, oral epithelium, intercellular junction proteins that maintain barrier strength, and also saliva and mucus. The barrier’s blood supply, neural connections, local immune responses, and the oral microbiome create the microenviroment, in which BSB operates. The BSB requires consideration of a number of additional variables, including innervation, blood supply, the presence of circulating metabolites in the vessels supplying the oral epithelium and salivary glands, as well as the volume of secreted saliva and its rheological properties, the composition of the oral microbiome, and the state of the immune system.

Article Details

How to Cite
Dyachenko, E., Sarf, E., & Bel’skaya, L. (2026). The Blood-Salivary Barrier as a Multifaceted System: a Review. Biomedical Chemistry: Research and Methods, 9(2), e00307. https://doi.org/10.18097/BMCRM00307
Issue
Vol. 9 No. 2 (2026)
Section
REVIEWS

References

  1. Fröhlich, E. (2002) Aufbau und funktion von blut-gewebeschranken [Structure and function of blood-tissue barriers]. Dtsch Med Wochenschr, 127, 2629-2634. DOI
  2. Ruvinskaya, G.R., Mukhamedzhanova, L.R. (2013) Hematosalivary barrier: morphofunctional features in norm and pathology. Prakticheskaya Meditsina, 4, 21-25.
  3. Huykin, S.V., Akmalova, G.M. (2015). The concept of hematosalivary barrier. Meditsinskiy Vestnik Bashkortostana, 5, 103-107.
  4. Waespe, N., Strebel, S., Marino, D., Mattiello, V., Muet, F., Nava, T., Schindera, C., Belle, F.N., Mader, L., Spoerri, A., Kuehni, C.E., Ansari, M. (2021) Predictors for participation in DNA self-sampling of childhood cancer survivors in Switzerland. BMC Medical Research Methodology, 21(1), 236. DOI
  5. Lin, G.C., Friedl, H.P., Grabner, S., Gerhartl, A., Neuhaus, W. (2024) Transport of non-steroidal anti-inflammatory drugs across an oral mucosa epithelium in vitro model. Pharmaceutics, 16(4), 543. DOI
  6. Čižmárová, B., Tomečková, V., Hubková, B., Hurajtová, A., Ohlasová, J., Birková, A. (2022) Salivary redox homeostasis in human health and disease. International Journal of Molecular Sciences, 23(17), 10076. DOI
  7. Cong, X., Mao, X. D., Wu, L. L., Yu, G.Y. (2024) The role and mechanism of tight junctions in the regulation of salivary gland secretion. Oral Diseases, 30(1), 3–22. DOI
  8. Lin, G.C., Küng, E., Smajlhodzic, M., Domazet, S., Friedl, H.P., Angerer, J., Wisgrill, L., Berger, A., Bingle, L., Peham, J.R., Neuhaus, W. (2021) Directed transport of CRP across in vitro models of the BSB strengthens the feasibility of salivary CRP as biomarker for neonatal sepsis. Pharmaceutics, 13(2), 256. DOI
  9. Thaler, J., Tripisciano, C., Nieuwland, R. (2024) Investigations on the hemostatic potential of physiological body fluids. Hamostaseologie, 44, 377-385. DOI
  10. Lin, G.C., Tevini, J., Mair, L., Friedl, H.P., Fuchs, D., Felder, T., Gostner, J.M., Neuhaus, W. (2024) Investigations towards tryptophan uptake and transport across an in vitro model of the oral mucosa epithelium. International Journal of Tryptophan Research, 17, 11786469241266312. DOI
  11. Gonçalves, A., Ambrósio, A.F., Fernandes, R. (2013) Regulation of claudins in blood-tissue barriers under physiological and pathological states. Tissue Barriers, 1(3), e24782. DOI
  12. Wen, Q., Tang, E.I., Gao, Y., Jesus, T.T., Chu, D.S., Lee, W.M., Wong, C.K.C., Liu, Y.X., Xiao, X., Silvestrini, B., Cheng, C.Y. (2018) Signaling pathways regulating blood-tissue barriers - Lesson from the testis. Biochimica et Biophysica Acta. Biomembranes, 1860(1), 141–153. DOI
  13. Hyvärinen, E., Savolainen, M., Mikkonen, J.J.W., Kullaa, A.M. (2021) Salivary metabolomics for diagnosis and monitoring diseases: challenges and possibilities. Metabolites, 11(9), 587. DOI
  14. Cui, Y., Yang, M., Zhu, J., Zhang, H., Duan, Z., Wang, S., Liao, Z., Liu, W. (2022) Developments in diagnostic applications of saliva in human organ diseases. Medicine in Novel Technology and Devices, 13, 100115. DOI
  15. Boroumand, M., Olianas, A., Cabras, T., Manconi, B., Fanni, D., Faa, G., Desiderio, C., Messana, I., Castagnola, M. (2021) Saliva, a bodily fluid with recognized and potential diagnostic applications. Journal of Separation Science, 44(19), 3677–3690. DOI
  16. Gartner, L.P. (1994) Oral anatomy and tissue types. Seminars in Dermatology, 13.
  17. Şenel, S. (2021) An overview of physical, microbiological and immune barriers of oral mucosa. International Journal of Molecular Sciences, 22(15), 7821. DOI
  18. Garant, P.R. (2003) Oral cells and tissues. New York State Dental Journal, 60.
  19. Wertz, P.W. (2021) Roles of lipids in the permeability barriers of skin and oral mucosa. International Journal of Molecular Sciences, 22(10), 5229. DOI
  20. Patel, V.N., Hoffman, M.P. (2014) Salivary gland development: a template for regeneration. Seminars in Cell Developmental Biology, 25-26, 52–60. DOI
  21. Lin, G.C., Smajlhodzic, M., Bandian, A.M., Friedl, H.P., Leitgeb, T., Oerter, S., Stadler, K., Giese, U., Peham, J.R., Bingle, L., Neuhaus, W. (2020) An in vitro barrier model of the human submandibular salivary gland epithelium based on a single cell clone of cell line HTB- 41: establishment and application for biomarker transport studies. Biomedicines, 8(9), 302. DOI
  22. Punj, A. (2019) Secretions of human salivary gland. In: Salivary Glands: New Approaches in Diagnostics and Treatment, edited by Güvenç, I.A. London: InTechOpen (Chapter 4).
  23. Kim, S.K., Nasjleti, C.E., Han, S.S. (1972) The secretion processes in mucous and serous secretory cells of the rat sublingual gland. Journal of Ultrastructure Research, 38(3), 371–389. DOI
  24. Holmberg, K.V., Hoffman, M.P. (2014) Anatomy, biogenesis and regeneration of salivary glands. Monographs in Oral Science, 24, 1–13. DOI
  25. Baker, O.J. (2016) Current trends in salivary gland tight junctions. Tissue Barriers, 4(3), e1162348. DOI
  26. de Paula, F., Teshima, T.H.N., Hsieh, R., Souza, M.M., Coutinho- Camillo, C.M., Nico, M.M.S., Lourenco, S.V. (2017) The expression of water channel proteins during human salivary gland development: a topographic study of aquaporins 1, 3 and 5. Journal of Molecular Histology, 48(5-6), 329–336. DOI
  27. Larsen, H.S., Aure, M.H., Peters, S.B., Larsen, M., Messelt, E.B., Kanli Galtung, H. (2011) Localization of AQP5 during development of the mouse submandibular salivary gland. Journal of Molecular Histology, 42(1), 71–81. DOI
  28. Hsieh, M.S., Jeng, Y.M., Lee, Y.H. (2019) Mist1: a novel nuclear marker for acinic cell carcinoma of the salivary gland. Virchows Archiv, 475(5), 617–624. DOI
  29. Pin, C.L., Bonvissuto, A.C., Konieczny, S.F. (2000) Mist1 expression is a common link among serous exocrine cells exhibiting regulated exocytosis. The Anatomical Record, 259(2), 157–167. DOI
  30. Valstar, M.H., de Bakker, B.S., Steenbakkers, R.J.H. M., de Jong, K.H., Smit, L.A., Klein Nulent, T.J.W., van Es, R.J.J., Hofland, I., de Keizer, B., Jasperse, B., Balm, A.J.M., van der Schaaf, A., Langendijk, J.A., Smeele, L.E., Vogel, W.V. (2021) The tubarial salivary glands: A potential new organ at risk for radiotherapy. Radiotherapy and oncology: journal of the European Society for Therapeutic Radiology and Oncology, 154, 292–298. DOI
  31. Dave, M. (2020) New salivary gland organs discovered. British Dental Journal, 229(9), 573. DOI
  32. Suvvari, T.K., Arigapudi, N. (2020) The tubarial glands: Discovered but not defined–A narrative review. Journal of Radiation and Cancer Research, 11, 140-141. DOI
  33. Singh, V., Reddy, K.C. (2021) Discovery of new organs in human throat: The tubarial salivary glands. Journal of the Anatomical Society of India, 70, 1-2. DOI
  34. Ebrahim, A., Reich, C., Wilde, K., Salim, A. M., Hyrcza, M.D., Willetts, L. (2025) A comprehensive analysis of the tubarial glands. Anatomical Record, 308(5), 1425–1437. DOI
  35. Zhu, W., Wang, Y., Guan, Y., Lu, Y., Li, Y., Sun, L., Wang, Y. (2024) Rapamycin can alleviate the submandibular gland pathology of Sjögren’s syndrome by limiting the activation of cGAS–STING signaling pathway. Inflammopharmacology, 32, 1113-31. DOI
  36. Sisto, M., Ribatti, D., Lisi, S. (2021) SMADS-mediate molecular mechanisms in Sjögren’s syndrome. International Journal of Molecular Sciences, 22(6), 3203. DOI
  37. Fouani, M., Basset, C. A., Jurjus, A. R., Leone, L.G., Tomasello, G., Leone, A. (2021) Salivary gland proteins alterations in the diabetic milieu. Journal of Molecular Histology, 52(5), 893–904. DOI
  38. Genco, R.J., Borgnakke, W.S. (2020) Diabetes as a potential risk for periodontitis: association studies. Periodontol, 2000, 83, 40-45. DOI
  39. Chen, S.Y., Wang, Y., Zhang, C.L., Yang, Z.M. (2020) Decreased basal and stimulated salivary parameters by histopathological lesions and secretory dysfunction of parotid and submandibular glands in rats with type 2 diabetes. Experimental and Therapeutic Medicine, 19(4), 2707–2719. DOI
  40. Klein Hesselink, E.N., Brouwers, A.H., de Jong, J.R., van der Horst-Schrivers, A.N., Coppes, R.P., Lefrandt, J.D., Jager, P.L., Vissink, A., Links, T.P. (2016) Effects of radioiodine treatment on salivary gland function in patients with differentiated thyroid carcinoma: a prospective study. Journal of Nuclear Medicine, 57(11), 1685–1691. DOI
  41. Jung, J.H., Lee, C.H., Son, S.H., Jeong, J.H., Jeong, S.Y., Lee, S.W., Lee, J., Ahn, B.C. (2017) High prevalence of thyroid disease and role of salivary gland scintigraphy in patients with xerostomia. Nuclear Medicine and Molecular Imaging, 51(2), 169–177. DOI
  42. Abetz, L.M., Savage, N.W. (2009) Burning mouth syndrome and psychological disorders. Australian Dental Journal, 54(2), 84–173. DOI
  43. Verhoeff, M.C., Koutris, M., Vries, R., Berendse, H.W., Dijk, K.D.V., Lobbezoo, F. (2023) Salivation in Parkinson’s disease: A scoping review. Gerodontology, 40(1), 26–38. DOI
  44. Jääskeläinen, S.K. (2018) Is burning mouth syndrome a neuropathic pain condition? Pain, 159(3), 610–613. DOI
  45. Sørensen, C.E., Hansen, N.L., Mortensen, E.L., Lauritzen, M., Osler, M., Pedersen, A.M. L. (2018) Hyposalivation and poor dental health status are potential correlates of age-related cognitive decline in late midlife in Danish men. Frontiers in Aging Neuroscience, 10, 10. DOI
  46. Yuan, Y., Jiao, B., Qu, L., Yang, D., Liu, R. (2023) The development of COVID-19 treatment. Frontiers in Immunology, 14, 1125246. DOI
  47. Meer, S. (2019) Human immunodeficiency virus and salivary gland pathology: an update. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 128(1), 52–59. DOI
  48. Domingues, N.B., Mariusso, M.R., Tanaka, M.H., Scarel- Caminaga, R.M., Mayer, M.P.A., Brighenti, F.L., Zuanon, Â.C.C., Ibuki, F.K., Nogueira, F.N., Giro, E.M.A. (2017) Reduced salivary flow rate and high levels of oxidative stress in whole saliva of children with Down syndrome. Special Care in Dentistry, 37(6), 269–276. DOI
  49. Seymen, F., Koruyucu, M., Toptanci, I. R., Balsak, S., Dedeoglu, S., Celepkolu, T., Shin, T.J., Hyun, H.K., Kim, Y.J., Kim, J.W. (2017) Novel FGF10 mutation in autosomal dominant aplasia of lacrimal and salivary glands. Clinical Oral Investigations, 21(1), 167–172. DOI
  50. Saeves, R., Reseland, J.E., Kvam, B.M., Sandvik, L., Nordgarden, H. (2012) Saliva in Prader-Willi syndrome: quantitative and qualitative characteristics. Archives of Oral Biology, 57(10), 1335–1341. DOI
  51. Vasconcelos, G., Stenehjem, J.S., Axelsson, S., Saeves, R. (2022) Craniofacial and dentoalveolar morphology in individuals with Prader-Willi syndrome: a case-control study. Orphanet Journal of Rare Diseases, 17(1), 77. DOI
  52. Ramírez, L., Sánchez, I., Muñoz, M., Martínez-Acitores, M.L., Garrido, E., Hernández, G., López-Pintor, R.M. (2023) Risk factors associated with xerostomia and reduced salivary flow in hypertensive patients. Oral Diseases, 29(3), 1299–1311. DOI
  53. Drent, M., Crouser, E. D., Grunewald, J. (2021) Challenges of Sarcoidosis and Its Management. The New England Journal of Medicine, 385(11), 1018–1032. DOI
  54. Arany, S., Kopycka-Kedzierawski, D.T., Caprio, T.V., Watson, G.E. (2021) Anticholinergic medication: Related dry mouth and effects on the salivary glands. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 132(6), 662–670. DOI
  55. Toan, N.K., Tai, N. C., Kim, S.A., Ahn, S.G. (2021) Choline acetyltransferase induces the functional regeneration of the salivary gland in aging SAMP1/Kl-/-Mice. International Journal of Molecular Sciences, 22(1), 404. DOI
  56. Song, W., Liu, H., Su, Y., Zhao, Q., Wang, X., Cheng, P., Wang, H. (2024) Current developments and opportunities of pluripotent stem cells-based therapies for salivary gland hypofunction. Frontiers in Cell and Developmental Biology, 12, 1346996. DOI
  57. Roussa, E. (2011) Channels and transporters in salivary glands. Cell and Tissue Research, 343(2), 263–287. DOI
  58. Catalán, M.A., Nakamoto, T., Melvin, J.E. (2009) The salivary gland fluid secretion mechanism. The Journal of Medical Investigation: JMI, 56 Suppl, 192–196. DOI
  59. Lapczuk-Romanska, J., Busch, D., Gieruszczak, E., Drozdzik, A., Piotrowska, K., Kowalczyk, R., Oswald, S., Drozdzik, M. (2019) Membrane transporters in human parotid gland-targeted proteomics approach. International Journal of Molecular Sciences, 20(19), 4825. DOI
  60. Sun, Q. F., Sun, Q. H., Du, J., Wang, S. (2008) Differential gene expression profiles of normal human parotid and submandibular glands. Oral Diseases, 14(6), 500–509. DOI
  61. Petersen, A.M., Small, C.M., Yan, Y.L., Wilson, C., Batzel, P., Bremiller, R.A., Buck, C.L., von Hippel, F.A., Cresko, W.A., Postlethwait, J.H. (2022) Evolution and developmental expression of the sodium-iodide symporter (NIS, slc5a5) gene family: Implications for perchlorate toxicology. Evolutionary Applications, 15(7), 1079– 1098. DOI
  62. Skrypnyk, M., Yatsenko, T., Riabets, O., Zuieva, O., Rodionova, I., Skikevych, M., Salama, Y., Osada, T., Tobita, M., Takahashi, S., Hattori, N., Takahashi, K., Hattori, K., Heissig, B. (2025) Potassium iodide induces apoptosis in salivary gland cancer cells. International Journal of Molecular Sciences, 26, 5199. DOI
  63. Angelow, S., Ahlstrom, R., Yu, A.S. (2008) Biology of claudins. American journal of physiology. Renal Physiology, 295(4), F867– F876. DOI
  64. Furuse, M., Tsukita, S. (2006). Claudins in occluding junctions of humans and flies. Trends in Cell Biology, 16(4), 181–188. https://doi. org/10.1016/j.tcb.2006.02.006
  65. Ikenouchi, J., Furuse, M., Furuse, K., Sasaki, H., Tsukita, S., Tsukita, S. (2005) Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. The Journal of Cell Biology, 171(6), 939–945. DOI
  66. Do, T.T., Nguyen, V.T., Nguyen, N.T.N., Duong, K.T.T., Nguyen, T.T.M., Le, D.N.T., Nguyen, T.H. (2024) A review of a breakdown in the barrier: tight junction dysfunction in dental diseases. Clinical, Cosmetic and Investigational Dentistry, 16, 513–531. DOI
  67. Hirabayashi, S., Tajima, M., Yao, I., Nishimura, W., Mori, H., Hata, Y. (2003) JAM4, a junctional cell adhesion molecule interacting with a tight junction protein, MAGI-1. Molecular and Cellular Biology, 23(12), 4267–4282. DOI
  68. Nasdala, I., Wolburg-Buchholz, K., Wolburg, H., Kuhn, A., Ebnet, K., Brachtendorf, G., Samulowitz, U., Kuster, B., Engelhardt, B., Vestweber, D., Butz, S. (2002) A transmembrane tight junction protein selectively expressed on endothelial cells and platelets. The Journal of Biological Chemistry, 277(18), 16294–16303. DOI
  69. Monteiro, A.C., Sumagin, R., Rankin, C.R., Leoni, G., Mina, M.J., Reiter, D.M., Stehle, T., Dermody, T.S., Schaefer, S.A., Hall, R.A., Nusrat, A., Parkos, C.A. (2013) JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function. Molecular Biology of the Cell, 24(18), 2849–2860. DOI
  70. Ebnet, K., Schulz, C.U., Meyer Zu Brickwedde, M.K., Pendl, G.G., Vestweber, D. (2000) Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1. The Journal of Biological Chemistry, 275(36), 27979–27988. DOI
  71. Gow, A., Davies, C., Southwood, C.M., Frolenkov, G., Chrustowski, M., Ng, L., Yamauchi, D., Marcus, D.C., Kachar, B. (2004) Deafness in Claudin 11-null mice reveals the critical contribution of basal cell tight junctions to stria vascularis function. The Journal of Neuroscience, 24(32), 7051–7062. DOI
  72. Tsukita, S., Furuse, M. (2002) Claudin-based barrier in simple and stratified cellular sheets. Current Opinion in Cell Biology, 14(5), 531–536. DOI
  73. Furuse, M., Hata, M., Furuse, K., Yoshida, Y., Haratake, A., Sugitani, Y., Noda, T., Kubo, A., Tsukita, S. (2002) Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. The Journal of Cell Biology, 156(6), 1099–1111. DOI
  74. Furuse, M. (2009) Knockout animals and natural mutations as experimental and diagnostic tool for studying tight junction functions in vivo. Biochimica et Biophysica Acta, 1788(4), 813–819. DOI
  75. Saitou, M., Furuse, M., Sasaki, H., Schulzke, J.D., Fromm, M., Takano, H., Noda, T., Tsukita, S. (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Molecular Biology of the Cell, 11(12), 4131–4142. DOI
  76. Shen, L., Turner, J.R. (2005) Actin depolymerization disrupts tight junctions via caveolae-mediated endocytosis. Molecular Biology of the Cell, 16(9), 3919–3936. DOI
  77. Yu, A.S., McCarthy, K.M., Francis, S.A., McCormack, J.M., Lai, J., Rogers, R.A., Lynch, R.D., Schneeberger, E.E. (2005) Knockdown of occludin expression leads to diverse phenotypic alterations in epithelial cells. American Journal of Physiology. Cell Physiology, 288(6), C1231–C1241. DOI
  78. Utech, M., Mennigen, R., Bruewer, M. (2010) Endocytosis and recycling of tight junction proteins in inflammation. Journal of Biomedicine Biotechnology, 2010, 484987. DOI
  79. Chen, Y.H., Lu, Q., Goodenough, D.A., Jeansonne, B. (2002) Nonreceptor tyrosine kinase c-Yes interacts with occludin during tight junction formation in canine kidney epithelial cells. Molecular Biology of the Cell, 13(4), 1227–1237. DOI
  80. Seth, A., Sheth, P., Elias, B. C., Rao, R. (2007) Protein phosphatases 2A and 1 interact with occludin and negatively regulate the assembly of tight junctions in the CACO-2 cell monolayer. The Journal of Biological Chemistry, 282(15), 11487–11498. DOI
  81. Furuse, M., Hirase, T., Itoh, M., Nagafuchi, A., Yonemura, S., Tsukita, S., Tsukita, S. (1993) Occludin: a novel integral membrane protein localizing at tight junctions. The Journal of Cell Biology, 123(6 Pt 2), 1777–1788. DOI
  82. Furuse, M. (2010) Molecular basis of the core structure of tight junctions. Cold Spring Harbor Perspectives in Biology, 2(1), a002907. DOI
  83. Ikenouchi, J., Sasaki, H., Tsukita, S., Furuse, M., Tsukita, S. (2008) Loss of occludin affects tricellular localization of tricellulin. Molecular Biology of the Cell, 19(11), 4687–4693. DOI
  84. Krug, S.M., Amasheh, S., Richter, J.F., Milatz, S., Günzel, D., Westphal, J.K., Huber, O., Schulzke, J.D., Fromm, M. (2009) Tricellulin forms a barrier to macromolecules in tricellular tight junctions without affecting ion permeability. Molecular Biology of the Cell, 20(16), 3713–3724. DOI
  85. Brummelkamp, T.R., Bernards, R., Agami, R. (2002) A system for stable expression of short interfering RNAs in mammalian cells. Science (New York, N.Y.), 296(5567), 550–553. DOI
  86. Riazuddin, S., Ahmed, Z.M., Fanning, A.S., Lagziel, A., Kitajiri, S., Ramzan, K., Khan, S.N., Chattaraj, P., Friedman, P.L., Anderson, J.M., Belyantseva, I.A., Forge, A., Riazuddin, S., Friedman, T.B. (2006) Tricellulin is a tight-junction protein necessary for hearing. American Journal of Human Genetics, 79(6), 1040–1051. DOI
  87. Umeda, K., Ikenouchi, J., Katahira-Tayama, S., Furuse, K., Sasaki, H., Nakayama, M., Matsui, T., Tsukita, S., Furuse, M., Tsukita, S. (2006) ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation. Cell, 126(4), 741–754. DOI
  88. Yamazaki, Y., Umeda, K., Wada, M., Nada, S., Okada, M., Tsukita, S., Tsukita, S. (2008) ZO-1- and ZO-2-dependent integration of myosin-2 to epithelial zonula adherens. Molecular Biology of the Cell, 19(9), 3801–3811. DOI
  89. Ikenouchi, J., Umeda, K., Tsukita, S., Furuse, M., Tsukita, S. (2007) Requirement of ZO-1 for the formation of belt-like adherens junctions during epithelial cell polarization. The Journal of Cell Biology, 176(6), 779–786. DOI
  90. Umeda, K., Matsui, T., Nakayama, M., Furuse, K., Sasaki, H., Furuse, M., Tsukita, S. (2004) Establishment and characterization of cultured epithelial cells lacking expression of ZO-1. The Journal of Biological Chemistry, 279(43), 44785–44794. DOI
  91. McNeil, E., Capaldo, C. T., Macara, I. G. (2006) Zonula occludens-1 function in the assembly of tight junctions in Madin- Darby canine kidney epithelial cells. Molecular Biology of the Cell, 17(4), 1922–1932. DOI
  92. Pinto-Dueñas, D.C., Hernández-Guzmán, C., Marsch, P.M., Wadurkar, A.S., Martín-Tapia, D., Alarcón, L., Vázquez-Victorio, G., Méndez-Méndez, J.V., Chanona-Pérez, J.J., Nangia, S., González- Mariscal, L. (2024) The role of ZO-2 in modulating JAM-A and γ-actin junctional recruitment, apical membrane and tight junction tension, and cell response to substrate stiffness and topography. International Journal of Molecular Sciences, 25(5), 2453. DOI
  93. Haskins, J., Gu, L., Wittchen, E.S., Hibbard, J., Stevenson, B.R. (1998) ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. The Journal of Cell Biology, 141(1), 199–208. DOI
  94. Liu, W., Cui, Y., Wei, J., Sun, J., Zheng, L., Xie, J. (2020) Gap junction-mediated cell-to-cell communication in oral development and oral diseases: a concise review of research progress. International Journal of Oral Science, 12(1), 17. DOI
  95. Krutovskikh, V., Yamasaki, H. (2000) Connexin gene mutations in human genetic diseases. Mutation Research, 462(2-3), 197–207. DOI
  96. Beyer, E.C., Berthoud, V.M. (2018) Gap junction gene and protein families: Connexins, innexins, and pannexins. Biochimica et Biophysica Acta. Biomembranes, 1860(1), 5–8. DOI
  97. Rodríguez-Sinovas, A., Ruiz-Meana, M., Denuc, A., García-Dorado, D. (2018) Mitochondrial Cx43, an important component of cardiac preconditioning. Biochimica et Biophysica Acta. Biomembranes, 1860(1), 174–181. DOI
  98. Zappitelli, T., Aubin, J.E. (2014) The “connexin” between bone cells and skeletal functions. Journal of Cellular Biochemistry, 115, 1646-1658. DOI
  99. Epifantseva, I., Shaw, R.M. (2018) Intracellular trafficking pathways of Cx43 gap junction channels. Biochimica et Biophysica Acta. Biomembranes, 1860(1), 40–47. DOI
  100. Pereda, A.E., Curti, S., Hoge, G., Cachope, R., Flores, C.E., Rash, J.E. (2013) Gap junction-mediated electrical transmission: regulatory mechanisms and plasticity. Biochimica et Biophysica Acta, 1828(1), 134–146. DOI
  101. Hervé, J.C., Derangeon, M. (2013) Gap-junction-mediated cellto- cell communication. Cell and Tissue Research, 352(1), 21–31. DOI
  102. Dupont, G., Combettes, L., Leybaert, L. (2007) Calcium dynamics: spatio-temporal organization from the subcellular to the organ level. International Review of Cytology, 261, 193–245. DOI
  103. Li, Y.Q., Tan, S.S., Wu, D., Zhang, Q., Wang, T., Zheng, G. (2025) The role of intracellular and extracellular copper compartmentalization in Alzheimer’s disease pathology and its implications for diagnosis and therapy. Frontiers in Neuroscience, 19, 1553064. DOI
  104. Al-Amoudi, A., Castaño-Diez, D., Devos, D.P., Russell, R.B., Johnson, G.T., Frangakis, A.S. (2011) The three-dimensional molecular structure of the desmosomal plaque. Proceedings of the National Academy of Sciences of the United States of America, 108(16), 6480–6485. DOI
  105. He, Y., Xu, M., Ouyang, J., Zhao, L., Ma, T., Zhang, X., Wang, R., Shang, H., Liang, G. (2025) Keratin-72 restricts HIV-1 infection in resting CD4+ T cells by sequestering capsids in intermediate filaments. Nature Communications, 16(1), 2998. DOI
  106. Parry, D.A.D. (2021) Structures of the ß-Keratin filaments and keratin intermediate filaments in the epidermal appendages of birds and reptiles (Sauropsids). Genes, 12(4), 591. DOI
  107. Louka, P., Kyriakou, C., Diakourti, I., Skourides, P. (2025) Plakophilin 3 is involved in basal body docking in multiciliated cells. International Journal of Molecular Sciences, 26(11), 5381. DOI
  108. Bass-Zubek, A.E., Godsel, L.M., Delmar, M., Green, K.J. (2009) Plakophilins: multifunctional scaffolds for adhesion and signaling. Current Opinion in Cell Biology, 21(5), 708–716. DOI
  109. Zhang, J., Gutierrez-Lara, E.J., Do, A., Nguyen, L., Nair, A., Selvan, N., Fenn, T., Adler, E., Khanna, R., Sheikh, F. (2025) Preclinical efficacy and safety of AAVrh10-based plakophilin-2 gene therapy (LX2020) as a treatment for arrhythmogenic cardiomyopathy. NPJ Regenerative Medicine, 10(1), 17. DOI
  110. Zou, Y., Lu, J., Lian, Z., Jia, J., Shen, J., Li, Q., Wong, J. M. J., Jin, K., Yan, W., Ren, X., Zhang, Y., Huang, C., Yang, H., Huang, F., Li, J., Zhai, J., Xu, Y., Xu, X., Yu, H., Jin, Y., Dai, Y. (2025) Modified mRNA treatment restores cardiac function in desmocollin- 2-deficient mouse models of arrhythmogenic right ventricular cardiomyopathy. Circulation, 151(25), 1780–1796. DOI
  111. Khan, K., Hardy, R., Haq, A., Ogunbiyi, O., Morton, D., Chidgey, M. (2006) Desmocollin switching in colorectal cancer. British Journal of Cancer, 95(10), 1367–1370. DOI
  112. Elias, P.M., Matsuyoshi, N., Wu, H., Lin, C., Wang, Z.H., Brown, B.E., Stanley, J.R. (2001) Desmoglein isoform distribution affects stratum corneum structure and function. The Journal of Cell Biology, 153(2), 243–249. DOI
  113. Yuan, Z.Y., Cheng, L.T., Wang, Z.F., Wu, Y.Q. (2021) Desmoplakin and clinical manifestations of desmoplakin cardiomyopathy. Chinese Medical Journal, 134(15), 1771–1779. DOI
  114. Choi, H. J., Weis, W. I. (2016) Purification and Structural Analysis of Desmoplakin. Methods in Enzymology, 569, 197–213. DOI
  115. Lialios, P., Alimperti, S. (2025) Role of E-cadherin in epithelial barrier dysfunction: implications for bacterial infection, inflammation, and disease pathogenesis. Frontiers in Cellular and Infection Microbiology, 15, 1506636. DOI
  116. Li, Y., Altorelli, N.L., Bahna, F., Honig, B., Shapiro, L., Palmer, A.G., 3rd (2013) Mechanism of E-cadherin dime