PERİODONTAL DURUMUN TÜKÜRÜK GROWTH ARREST-SPECIFIC PROTEIN 6(GAS6) DÜZEYİ ÜZERİNE ETKİSİNİN İNCELENMESİ

Year 2020, Volume: 30 Issue: 3, 379 - 385, 15.07.2020

Nur Balcı Arten Dyrmishi Metin Çetin Ali Çekici

https://doi.org/10.17567/ataunidfd.674684

Abstract

Giriş: Periodontitis, diş destek dokularında yıkımla karakterize olan ve değişik formları bulunan kronik inflamatuar bir hastalıktır. Growth arrest-specific protein 6(Gas6), hücre proliferasyonunu, adezyonunu, migrasyonunu, apoptotik hücrelerin makrofajlar tarafından fagositozunu ve adiposit gelişimini düzenleyen; obezite, diyabetes mellitus ve aterosklerozis gibi kronik hastalıkların patogenezinde rol alan bir proteindir. Bilgimiz dahilinde literatürde Gas6 proteinin periodontal hastalık ile ilişkisi araştırılmamıştır. Bu çalışmanın amacı, Gas6 proteininin periodontal doku yıkımındaki rolünün araştırılması ve bu molekülün periodontal hastalık patogenezindeki yerinin aydınlatılmasıdır.
Gereç ve Yöntem: Periodontoloji Kliniğine tedavi için başvuran ve periodontitis (evre III, derece B, generalize) tanısı konmuş sistemik olarak sağlıklı (8 kadın, 13 erkek) 20 hasta ile sistemik ve periodontal olarak sağlıklı (7 kadın, 12 erkek) 20 birey çalışmaya dahil edilmiştir. Tükürük örnekleri, klinik periodontal indekslerin ölçümleri (Sondalamada cep derinliği (SCD), sondalamada kanama indeksi (SKİ), dişeti çekilmesi (DÇ), plak indeksi (Pİ) ve klinik ataçman kaybı (KAK)) öncesinde alınmıştır. Toplanan tükürük örneklerinde Gas6 anti-enflamtuar proteini ELISA yöntemi ile incelenmiştir. Sonuçlar IBM SPSS Statistics 22 programı kullanılarak Mann Whitney U testi, Continuity (Yates) Düzeltmesi ve Ki-Kare testi ile değerlendirilmiştir.
Bulgular: Periodontitis hastalarının tüm klinik periodontal indeks değerleri, sağlıklı bireylerden istatistiksel olarak anlamlı yüksek bulunmuştur (p:0.001;p<0.01). Tükürükteki Gas6 protein düzeyi periodontitisli ve sağlıklı bireyler arasında istatistiksel olarak anlamlı bir fark göstermemiştir.
Sonuç: Bu çalışmanın sonuçlarına göre periodontitisli bireylerin tükürüğünde Gas6 proteini tespit edilmiştir. Ancak Gas6’nın periodontitisin patogenezinde olası bir rolünün olup olmadığı tartışmalıdır. Serum ve dişeti oluğu sıvısı örneklerinin de dahil edildiği ve anti-enflamatuar proteinler ile pro-enflamatuar sitokinler arası ilişkinin değerlendirilebileceği ileri çalışmalara ihtiyaç vardır.
Anahtar Kelimeler: Gas6, Periodontitis, Tükürük

Evaluation of the effect of periodontal status on saliva Growth arrest-specific protein 6(Gas6)

Aim: Periodontitis is a chronic inflammatory disease which is characterized with destruction of tooth supporting tissues and have various forms. Growth arrest-specific protein 6(Gas6), is a protein that regulates cell proliferation, adhesion, migration, phagocytosis of apoptotic cells by macrophages and adipocyte development and also has roles on the pathogenesis of chronic diseases such as obesity, diabetes mellitus and atherosclerosis. To the best of our knowledge, the relationship between Gas6 protein and periodontal disease has not been investigated in the literature. The aim of this study was to investigate the role of Gas6 protein in periodontal tissue destruction and to elucidate the role of this molecule in the pathogenesis of periodontal disease.
Material and Method: Twenty systemically healthy (8 female, 13 male) patients with periodontitis (stage III, grade B, generalized) admitted to the periodontology clinic for treatment and systemically and periodontally healthy 20 individuals (7 female, 12 male) were included in the study. Saliva samples were taken before the measurement of clinical periodontal indices (Probing pocket depth(PPD), bleeding on probing (BOP), gingival recession (GR), plaque index (PI) and clinical attachment loss (CAL). Gas6 anti-inflammatory protein in saliva samples was examined by ELISA method. Results were evaluated by Mann Whitney U test, Continuity (Yates) correction and Chi-Square test using IBM SPSS Statistics 22 program.
Results: All clinical periodontal index values of patients with periodontitis were significantly higher than healthy subjects (p: 0.001; p <0.01). Gas6 protein level in saliva did not show a statistically significant difference between periodontitis and healthy individuals.
Conclusion: According to the results of this study, Gas6 protein was detected in the saliva of periodontitis patients. However, it is controversial whether Gas6 has a possible role in the pathogenesis of periodontitis. Further studies are needed to include serum and gingival fluid samples and to evaluate the relationship between anti-inflammatory proteins and pro-inflammatory cytokines.
Key Words: Gas6, Periodontitis, Saliva

Keywords

Gas6, Periodontitis, Tükürük

References

• 1. Fernandez-Fernandez L, Bellido-Martin L, Garcia de Frutos P. Growth arrestspecifi c gene 6 (GAS6). An outline of its role in haemostasis and infl ammation. Thromb Haemost 2008;100:604-610.
• 2. Carlo Smirne, Cristina Rigamonti, Carla De Benedittis, et al.Gas6/TAM Signaling Components as Novel Biomarkers of Liver Fibrosis. Disease Markers 2019;Article ID 2304931, 15 pages, https://doi.org/10.1155/2019/2304931.
• 3. Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. Journal of Clinical Investigation 2011; 121(6):2111–2117.
• 4. Hirschi KM, Tsai KYF, Davis T, Clark JC, Knowlton MN, Bikman BT, Reynolds PR, Arroyo JA.Growth Arrest Specific Protein (Gas)-6/AXL Signaling Induces Preeclampsia (PE) in Rats.: Biol Reprod. 2019; Jul 26. pii: ioz140. doi: 10.1093/biolre/ioz140. [Epub ahead of print]
• 5. Feng X, Deng T, Zhang Y, Su S, Wei C, Han D. Lipopolysaccharide inhibits macrophage phagocytosis of apoptotic neutrophils by regulating the production of tumour necrosis factor a and growth arrest-specific gene 6. Immunology 2011;132: 287–295.
• 6. Alciato F, Sainaghi PP, Sola D, Castello L, Avanzi GC. TNF-α, IL-6, and IL-1 expression is inhibited by GAS6 in monocytes/macrophages . J. Leukoc. Biol. 2010; 87: 869–875.
• 7. Esmon CT. The interactions between inflammation and coagulation. Br J Haematol. 2005; 131:417-430.
• 8. Könönen E, Gursoy M, Gursoy UK. Periodontitis: A Multifaceted Disease of Tooth Supporting Tissues.J.Clin. Med.2019,8(8), 1135.
• 9. Teng YT. The role of acquired immunity and periodontal disease progression. Crit Rev Oral Biol Med. 2003;14(4):237-52.
• 10. Gaffen SL, Hajishengallis G. New inflammatory cytokine on the block: re-thinking periodontal disease and the Th1/Th2 paradigm in the context of Th17 cells and IL-17. J Dent Res. 2008; 87:817–28.
• 11. Eskan MA, Jotwani R, Abe T, Chmelar J, Lim J.H, Liang S ve ark. The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss. Nat Immunol. 2012;13:465–473.
• 12. Loesche WJ, Grossman NS. Periodontal disease as a specific, albeit chronic, infection: diagnosis and treatment. Clin Microbiol Rev. 2001;14: 727–52.
• 13. Mealey BL, Moritz AJ. Hormonal influences: effects of diabetes mellitus and endogenous female sex steroid hormones on the periodontium. Periodontology 2000. 2003;32: 59-81.
• 14. Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends in Immunology. 2014;35(1):3-11.
• 15. Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol 2010;11:785-797.
• 16. Kobayashi T, Ito S, Yasuda K, Kuroda T, Yamamoto K, Sugita N, et al. The combined genotypes of stimulatory and inhibitory Fc gamma receptors associated with systemic lupus erythematosus and periodontitis in Japanese adults. Journal of Periodontology 2007;78:467-474.
• 17. Elliott M.R, Ravichandran K.S. Clearance of apoptotic cells: implications in health and disease. Journal of Cell Biology. 2010; 189(7): 1059–1070.
• 18. G Caton J, Armitage G, Berglundh T, Chapple ILC, Jepsen S, S Kornman K. et al. A new classification scheme for periodontal and peri-implant diseases and conditions - Introduction and key changes from the 1999 classification. J Periodontol2018;89:S1-S8.
• 19. Gokturk O, Yarkac Ucan F, Ozelci F. Dişeti iltihaplı ve periodontal sağlikli bireylerde tükürük kortizol ve algılanan stres düzeylerinin değerlendirilmesi. J Dent Fac Atatürk Uni 2019; 29(2): 206-212
• 20. Stepan H, Richter J, Kley K, Jank A, Schaarschmidt W, Ebert T, et al. Serum levels of growth arrest specific protein 6 are increased in preeclampsia. Regulatory Peptides 2013;182: 7–11.
• 21. Linger RM, Keating AK, Earp HS, Graham DK: TAM receptor tyrosine kinases: biologic functions, signaling, and potential therapeutic targeting in human cancer. Adv Cancer Res 2008;100:35-83.
• 22. Angelillo-Scherrer A, de Frutos P, Aparicio C, Melis E, Savi P, Lupu F et al. Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nat Med 2001;7:215-221.
• 23. Lu Q, Lemke G. Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science 2001;293:306-311.
• 24. Scott RS, McMahon EJ, Pop SM, Reap EA, Caricchio R, Cohen PL, et al. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature 2001; 411:207-211.
• 25. Laurence S, Lemarie C, Blostein M. Growth arrest-Specific Gene 6(Gas-6) and Vascular Hemostasis.American Society for Nutrition 3 2012;196-203.
• 26. Ekman C, Linder A, Akesson P, Dahlbäck B. Plasma concentrations of Gas6 (growth arrest specific protein 6) and its soluble tyrosine kinase receptor Axl in sepsis and systemic inflammatory response syndromes. Crit Care 2010; 14: R158.
• 27. Balogh I, Hafizi S, Stenhoff J, Hansson K, Dahlbäck B. Analysis of Gas6 in human platelets and plasma. Arterioscler Thromb Vasc Biol 2005;25: 1280-1286.
• 28. Kuo FC, Hung YJ,Shieh YS, Hsieh CH, Hsiao FC, Lee CH. The levels of plasma growth arrest –spesific protein 6 is associated with insülin sensitivity and inflammation in women. Diabetes research and clinical practice 2014;304-309.
• 29. Eroglu M,Özakpınar O.B, Turkgeldi L,Sahin S, Herkiloglu D, Durukan B et al.Plasma levels of growth arrest specific protein 6 are increased in idiopathic recurrent pregnancy loss.European Review for Medical and Pharmacological Sciences 2014;18:1554-1558.
• 30. Thornton P, Douglas J. Coagulation in pregnancy. Best Pract Res Clin Obstet Gynaecol 2010; 24:339-352.
• 31. Hsiao FC, Lin YF, Hsieh PS, Chu NF.Circulating growth arrest-specific 6 protein is associated with adiposity, systemic inflammation, and insulin resistance among overweight and obese adolescents.J Clin Endocrinol Metab 2013;98(2):E267-74.
• 32. Borgel D, Clauser S, Bornstain C, Bièche I, Bissery A, Remones V, et al. Elevated growth-arrest-specific protein 6 plasma levels in patients with severe sepsis. Crit Care Med 2006;34:219–22.
• 33. Goyal L, Bey A, Gupta ND, Sharma VK. Comparative evaluation of serum C-reactive protein levels in chronic and aggressive periodontitis patients and association with periodontal disease severity. Contemp Clin Dent 2014;5(4):484-8.
• 34. Ishikawa M, Sonobe M, Nakayama E, Kobayashi M, Kikuchi R, Kitamura J, et al. Higher expression of receptor tyrosine kinase Axl, and differential expression of its ligand, Gas6, predict poor survival in lung adenocarcinoma patients. Ann Surg Oncol.2013;20Suppl 3:S467-76.
• 35. Whitman SP, Kohlschmidt J, Maharry K, Volinia S, Mrózek K, Nicolet D, et al. GAS6 expression identifies high-risk adult AML patients: potential implications for therapy. Leukemia.2014;28(6):1252-82.