Journal of Oral Medicine and Pain

Korean Academy of Orofacial Pain and Oral Medicine (대한안면통증구강내과학회)
권호 표지
DOI QR코드

DOI QR Code

Role of Homeostatic Changes in Salivary Gland Acinar Cells in Primary Sjögren's Syndrome: A Review

  • Jin-Seok Byun (Department of Oral Medicine, School of Dentistry, Kyungpook National University)
  • Received : 2023.06.07
  • Accepted : 2023.06.14
  • Published : 2023.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Primary Sjögren's syndrome (pSS) is an autoimmune progressive disease characterized by dysfunction and inflammation of the salivary glands. The underlying mechanisms of salivary gland involvement in pSS remain unclear, and researchers have primarily focused on immunological phenomena, making it difficult to distinguish between the cause and effect of the disease. Consequently, our research aims to directly investigate changes in homeostasis occurring in acinar cells, specifically in the context of muscarinic signaling, mucins, aquaporins, and forkhead box protein O1, to elucidate the initial step of pSS. We compare the disease-related phenomena observed in salivary gland acinar cells in pSS with the overall process of salivary secretion.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) RS-2023-00208416.

References

  1. Brito-Zeron P, Baldini C, Bootsma H, et al. Sjogren syndrome. Nat Rev Dis Primers 2016;2:16047. 
  2. Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjogren's syndrome: a consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis 2017;76:9-16.  https://doi.org/10.1136/annrheumdis-2016-210571
  3. Shiboski SC, Shiboski CH, Criswell L, et al. American College of Rheumatology classification criteria for Sjogren's syndrome: a data-driven, expert consensus approach in the Sjogren's International Collaborative Clinical Alliance cohort. Arthritis Care Res (Hoboken) 2012;64:475-87.  https://doi.org/10.1002/acr.21591
  4. Aqrawi LA, Jensen JL, Oijordsbakken G, et al. Signalling pathways identified in salivary glands from primary Sjogren's syndrome patients reveal enhanced adipose tissue development. Autoimmunity 2018;51:135-146.  https://doi.org/10.1080/08916934.2018.1446525
  5. Tsunawaki S, Nakamura S, Ohyama Y, et al. Possible function of salivary gland epithelial cells as nonprofessional antigen-presenting cells in the development of Sjogren's syndrome. J Rheumatol 2002;29:1884-1896. 
  6. Tang Y, Zhou Y, Wang X, et al. The role of epithelial cells in the immunopathogenesis of Sjogren's syndrome. J Leukoc Biol 2023;qiad049. 
  7. Verstappen GM, Pringle S, Bootsma H, Kroese FGM. Epithelialimmune cell interplay in primary Sjogren syndrome salivary gland pathogenesis. Nat Rev Rheumatol 2021;17:333-348.  https://doi.org/10.1038/s41584-021-00605-2
  8. Molina C, Alliende C, Aguilera S, et al. Basal lamina disorganisation of the acini and ducts of labial salivary glands from patients with Sjogren's syndrome: association with mononuclear cell infiltration. Ann Rheum Dis 2006;65:178-183.  https://doi.org/10.1136/ard.2004.033837
  9. McArthur CP, Fox NW,Kragel P. Monoclonal antibody detection of laminin in minor salivary glands of patients with Sjogren's syndrome. J Autoimmun 1993;6:649-661.  https://doi.org/10.1006/jaut.1993.1053
  10. Nikolov NP, Illei GG. Pathogenesis of Sjogren's syndrome. Curr Opin Rheumatol 2009;21:465-470.  https://doi.org/10.1097/BOR.0b013e32832eba21
  11. Perez P, Goicovich E, Alliende C, et al. Differential expression of matrix metalloproteinases in labial salivary glands of patients with primary Sjogren's syndrome. Arthritis Rheum 2000;43:2807-2817.  https://doi.org/10.1002/1529-0131(200012)43:12<2807::AID-ANR22>3.0.CO;2-M
  12. Li N, Li YS, Hu JW, et al. A link between mitochondrial dysfunction and the immune microenvironment of salivary glands in primary Sjogren's syndrome. Front Immunol 2022;13:845209. 
  13. Dawson L, Tobin A, Smith P, Gordon T. Antimuscarinic antibodies in Sjogren's syndrome: where are we, and where are we going? Arthritis Rheum 2005;52:2984-2995.  https://doi.org/10.1002/art.21347
  14. Li J, Ha YM, Ku NY, et al. Inhibitory effects of autoantibodies on the muscarinic receptors in Sjogren's syndrome. Lab Invest 2004;84:1430-1438.  https://doi.org/10.1038/labinvest.3700173
  15. Matsui M, Motomura D, Karasawa H, et al. Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype. Proc Natl Acad Sci U S A 2000;97:9579-9584.  https://doi.org/10.1073/pnas.97.17.9579
  16. Lee BH, Gauna AE, Perez G, et al. Autoantibodies against muscarinic type 3 receptor in Sjogren's syndrome inhibit aquaporin 5 trafficking. PLoS One 2013;8:e53113. 
  17. Chaudhury NM, Proctor GB, Karlsson NG, Carpenter GH, Flowers SA. Reduced mucin-7 (Muc7) sialylation and altered saliva rheology in Sjogren's syndrome associated oral dryness. Mol Cell Proteomics 2016;15:1048-1059.  https://doi.org/10.1074/mcp.M115.052993
  18. Chaudhury NMA, Shirlaw P, Pramanik R, Carpenter GH, Proctor GB. Changes in saliva rheological properties and mucin glycosylation in dry mouth. J Dent Res 2015;94:1660-1667.  https://doi.org/10.1177/0022034515609070
  19. Barrera MJ, Aguilera S, Veerman E, et al. Salivary mucins induce a toll-like receptor 4-mediated pro-inflammatory response in human submandibular salivary cells: are mucins involved in Sjogren's syndrome? Rheumatology (Oxford) 2015;54:1518-1527.  https://doi.org/10.1093/rheumatology/kev026
  20. Barrera MJ, Sanchez M, Aguilera S, et al. Aberrant localization of fusion receptors involved in regulated exocytosis in salivary glands of Sjogren's syndrome patients is linked to ectopic mucin secretion. J Autoimmun 2012;39:83-92.  https://doi.org/10.1016/j.jaut.2012.01.011
  21. Castro I, Albornoz N, Aguilera S, et al. Aberrant MUC1 accumulation in salivary glands of Sjogren's syndrome patients is reversed by TUDCA in vitro. Rheumatology (Oxford) 2020;59:742-753.  https://doi.org/10.1093/rheumatology/kez316
  22. Morishita Y, Sakube Y, Sasaki S, Ishibashi K. Molecular mechanisms and drug development in aquaporin water channel diseases: aquaporin superfamily (superaquaporins): expansion of aquaporins restricted to multicellular organisms. J Pharmacol Sci 2004;96:276-279.  https://doi.org/10.1254/jphs.FMJ04004X7
  23. Gresz V, Kwon TH, Hurley PT, et al. Identification and localization of aquaporin water channels in human salivary glands. Am J Physiol Gastrointest Liver Physiol 2001;281:G247-254.  https://doi.org/10.1152/ajpgi.2001.281.1.G247
  24. Beroukas D, Hiscock J, Gannon BJ, Jonsson R, Gordon TP, Waterman SA. Selective down-regulation of aquaporin-1 in salivary glands in primary Sjogren's syndrome. Lab Invest 2002;82:1547-1552.  https://doi.org/10.1097/01.LAB.0000038502.42845.9E
  25. Alam J, Choi YS, Koh JH, et al. Detection of Autoantibodies against Aquaporin-1 in the Sera of Patients with Primary Sjogren's Syndrome. Immune Netw 2017;17:103-109.  https://doi.org/10.4110/in.2017.17.2.103
  26. Verkman A, Yang B, Song Y, Manley GT, Ma T. Role of water channels in fluid transport studied by phenotype analysis of aquaporin knockout mice. Exp Physiol 2000;85 Spec No:233S-241S.  https://doi.org/10.1111/j.1469-445X.2000.tb00028.x
  27. Ichiyama T, Nakatani E, Tatsumi K, et al. Expression of aquaporin 3 and 5 as a potential marker for distinguishing dry mouth from Sjogren's syndrome. J Oral Sci 2018;60:212-220.  https://doi.org/10.2334/josnusd.17-0150
  28. Alam J, Koh JH, Kim N, et al. Detection of autoantibodies against aquaporin-5 in the sera of patients with primary Sjogren's syndrome. Immunol Res 2016;64:848-856.  https://doi.org/10.1007/s12026-016-8786-x
  29. Soyfoo MS, De Vriese C, Debaix H, et al. Modified aquaporin 5 expression and distribution in submandibular glands from NOD mice displaying autoimmune exocrinopathy. Arthritis Rheum 2007;56:2566-2574.  https://doi.org/10.1002/art.22826
  30. Steinfeld S, Cogan E, King LS, Agre P, Kiss R, Delporte C. Abnormal distribution of aquaporin-5 water channel protein in salivary glands from Sjogren's syndrome patients. Lab Invest 2001;81:143-148.  https://doi.org/10.1038/labinvest.3780221
  31. Enger TB, Aure MH, Jensen JL, Galtung HK. Calcium signaling and cell volume regulation are altered in Sjogren's syndrome. Acta Odontol Scand 2014;72:549-556.  https://doi.org/10.3109/00016357.2013.879995
  32. Lai Z, Yin H, Cabrera-Perez J, et al. Aquaporin gene therapy corrects Sjogren's syndrome phenotype in mice. Proc Natl Acad Sci U S A 2016;113:5694-5699.  https://doi.org/10.1073/pnas.1601992113
  33. Enger TB, Aure MH, Jensen JL, Galtung HK. Calcium signaling and cell volume regulation are altered in Sjogren's Syndrome. Acta Odontol Scand 2014;72:549-556.  https://doi.org/10.3109/00016357.2013.879995
  34. Soyfoo MS, Konno A, Bolaky N, et al. Link between inflammation and aquaporin-5 distribution in submandibular gland in Sjogren's syndrome? Oral Dis 2012;18:568-574.  https://doi.org/10.1111/j.1601-0825.2012.01909.x
  35. Sandhya P, Theyilamannil Kurien B, Danda D, Hal Scofield R. Update on pathogenesis of Sjogren's syndrome. Curr Rheumatol Rev 2017;13:5-22.  https://doi.org/10.2174/1573397112666160714164149
  36. Argyropoulou OD, Valentini E, Ferro F, et al. One year in review 2018: Sjogren's syndrome. Clin Exp Rheumatol 2018;36 Suppl 112:14-26. 
  37. Verstappen GM, Corneth OB, Bootsma H, Kroese FG. Th17 cells in primary Sjogren's syndrome: pathogenicity and plasticity. J Autoimmun 2018;87:16-25.  https://doi.org/10.1016/j.jaut.2017.11.003
  38. Lee SM, Lee SW, Kang M, et al. FoxO1 as a Regulator of Aquaporin 5 Expression in the Salivary Gland. J Dent Res 2021;100:1281-1288.  https://doi.org/10.1177/00220345211003490
  39. Hosaka T, Biggs WH 3rd, Tieu D, et al. Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proc Natl Acad Sci U S A 2004;101:2975-2980.  https://doi.org/10.1073/pnas.0400093101
  40. Tothova Z, Kollipara R, Huntly BJ, et al. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 2007;128:325-339.  https://doi.org/10.1016/j.cell.2007.01.003
  41. Puig O, Tjian R. Transcriptional feedback control of insulin receptor by dFOXO/FOXO1. Genes Dev 2005;19:2435-2446. https://doi.org/10.1101/gad.1340505