Published September 9, 2022 | Version v1
Journal article Open

COMPARISON OF BiP AND Hsp70i AS MARKERS OF ULFOLDED PROTEIN RESPONSE (UPR) IN SEGMENTAL AND NONSEGMENTAL VITILIGO

Authors/Creators

  • 1. Department of Clinical Dermatology and Venereology, Kepanjen Kanjuruhan Hospital, Malang, Indonesia.
  • 2. Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Dr Saiful Anwar General Hospital, Malang, Indonesia.
  • 3. Clinical Parasitology Department, Faculty of Medicine, Universitas Brawijaya, Dr Saiful Anwar General Hospital, Malang, Indonesia.
  • 4. Department of Dermatology and Venereology, Faculty of Medicine, Universitas Brawijaya, Dr Saiful Anwar General Hospital, Malang, Indonesia.

Description

Abstract

 

Background: Unfolded protein response (UPR) is an important genomic response to endoplasmic reticulum (ER) stress. ER chaperones, binding immunoglobulin protein (BiP), and heat shock protein 70 inducible (Hsp70i) play critical roles in cell survival because they cause cell damage and melanocyte apoptosis. 

Aim: Our study aims to compare BiP and Hsp70i as markers of UPR in patients with segmental vitiligo (SV) and non-segmental vitiligo (NSV). 

Material and methods: The subjects were composed of 64 patients diagnosed with vitiligo, of whom 33 had NSV and 31 had SV. Skin biopsy and immunofluorescence were performed. We used BiP and Hsp70i as markers of UPR. Appropriate statistical methods were used to analyze the data. 

Results: UPR-BiP expression and UPR-Hsp70i in the SV group was 2.66 ± 3.07 and 3.85 ± 4.92, respectively, with a p-value of 0.001 (<α = 0.05). In the NSV group UPR-BiP expression and UPR-Hsp70i and was 12.55 ± 11.85 and 14.79 ± 14.72, respectively, with a p-value of 0.001 (<α = 0.05). UPR expression using the Hsp70i marker in both NSV and SV groups was higher than it was using the BiP marker. The relationship between UPR-Hsp70i expression and UPR-BiP expression in the SV and NSV group was significant (p <0.05) and positive. 

Conclusion: Hsp70i is superior to BiP as a marker for expressing UPR.

 

Keywords: Hsp701, BiP, Segmental and Non-Segmental Vitiligo

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References

  • 1. Boniface K, Seneschal J, Picardo M, Taieb A. Vitiligo: focus on clinical aspects, immunopathogenesis, and therapy. Clin Rev Allergy Immunol. 2018;54(1):52-67. doi: 10.1007/s12016-017-8622-7.
  • 2. Habib A. Clinical profile of segmental vitiligo in a group of Pakistani. Pak Armed Forces Med J. 2019;69(3):495-99.
  • 3. Karagaiah P, Schwartz RA, Lotti T, Wollina U, Grabbe S, Goldust M. Biologic and targeted therapeutics in vitiligo. J Cosmet Dermatol. 2022.
  • 4. Faraj S, Kemp EH, Gawkrodger DJ. Patho-immunological mechanisms of vitiligo: the role of the innate and adaptive immunities and environmental stress factors. Clin Exp Immunol. 2022;207(1):27-43.
  • 5. Thakur V, Bishnoi A, Vinay K, Kumaran SM, Parsad D. Vitiligo: translational research and effective therapeutic strategies. Pigment Cell Melanoma Res. 2021;34(4):814-826.
  • 6. Van Geel N, Van Haverbeke C, Speeckaert R. Pathofisiology of segmental vitiligo. Vitiligo. 2019:333-336. doi: 10.1007/978-3-319-62960-5_32.
  • 7. Frisoli ML, Essien K, Harris JE. Vitiligo: mechanisms of pathogenesis and treatment. Annu Rev Immunol. 2020;38(1). doi: 10.1146/annurev-immunol-100919-023531.
  • 8. Wang Y, Li S, Li C. Perspective of new advances in the pathogenesis of vitiligo: from oxidatve stress to autoimmunity. Med Science Monit. 2019;25:1017-1023. doi: 10.12659/MSM.914898.
  • 9. Picardo M. Pathophysiology overview. Vitiligo, 2019:189-192. doi: 10.1007/978-3-319-62960-5_20.
  • 10. Bergqvist C, Ezzdine K. Vitiligo: a review. Review Article of Dermatology. 2020:1-22. doi: 10.1159/000506103.
  • 11. Jadeja SD, Mayatra JM, Vaishnav J, Shukla N, Begum R. A concise review on the role of endoplasmic reticulum stress in the development of autoimmunity in vitiligo pathogenesis. Front Immunol. 2021;11:624566.
  • 12. Martelli AM, Paganelli F, Chiarini F, Evangelisti C, McCubrey JA. The unfolded protein response: a novel therapeutic target in acute leukemias. Cancers. 2020;12(2):333. doi:10.3390/cancers12020333
  • 13. Siwecka N, Rozpędek W, Pytel D, Wawrzynkiewicz A, Dziki A, Dziki Ł, Majsterek I, et al. Dual role of endoplasmic reticulum stress-mediated unfolded protein response signaling pathway in carcinogenesis. Int J Mol Sci. 2019;20(18):4354. doi:10.3390/ijms20184354.
  • 14. Hetz C, Zhang K, Kaufman RJ. Mechanisms, regulation and functions of the unfolded protein response. Nat Rev Mol Cell Biol. 2020;21:421-438. https://doi.org/10.1038/s41580-020-0250-z.
  • 15. Park K, Lee SE, Shin K-Oh, Uchida Y. Insights into the role of endoplasmic reticulum stress in skin function and assciated diseases. Review Article. FEBS J. 2019:413-425. doi: 10.1111/febs.1473.
  • 16. Kundu RV, Mhlaba JM, Rangel SM, Poole IC. The convergence theory for vitiligo: A reappraisal. Exp Dermatol. 2018. doi: 10.1111/exd.13677.
  • 17. Chen X, Guo W, Chang Y, Chen J, Kang P, Yi X, Li C, et al. Oxidative stress-induced IL-15 trans-presentation in keratinocytes contributes to CD8+ T cells activation via JAK-STAT pathway in vitiligo. Free Radic Biol Med. 2019;139:80-91.
  • 18. Abbas AK, Lichtman AH, Pillai S. Cellular and mollecular immunology. 9th ed. Winsland: Elsevier.
  • 19. Mathachan S, Khurana A, Gautam R, Kulhari A, Sharma L, Sardana K. Does oxidative stress correlate with disease activity and severity in vitiligo? An analytical study. J Cosmet Dermatol. 2020. doi:10.1111/jocd.13499.
  • 20. Tang L, Li J, Fu W, Wu W, Xu J. Suppression of FADS1 induces ROS generation, cell cycle arrest, and apoptosis in melanocytes: implications for vitiligo. Aging. 2019;11(24):11829.
  • 21. Singh M, Kotnis A, Jadeja SD, Mondal A, Mansuri MS, Begum R. Cytokines: the yin and yang of vitiligo pathogenesis. Expert Rev Clin Immunol. 2018. doi:10.1080/1744666x.2019.1550358.
  • 22. Manga P, Elbuluk, Orlow SJ. Recent advances in understanding vitiligo. F1000 Research, 2016;5:2234. doi:10.12688/f1000research.8976.1.
  • 23. Bakry O, Elhefnawy S, Seliet E, Omar MA. Determination of oxidative stress in vitiligo by measuring superoxide dismutase levels in vitiliginous skin. Original Article, 2020;33(1):262-266. doi: 10.4103/mmj.mmj_246_18.
  • 24. Smith JA. Regulation of cytokine production by the unfolded protein response; implications for infection and autoimmunity. Front Immunol. 2018:9. doi:10.3389/fimmu.2018.00422.
  • 25. Sarma N. Nonsegmental vitiligo follows Blaschko's lines and embryonic pigmentary segments. Indian J Dermatol Venereol Leprol. 2020;86(4).
  • 26. Khaitan BK, Sindhuja T. Autoimmunity in vitiligo: Therapeutic implications and opportunities. Autoimmun Rev. 2021:102932. doi:10.1016/j.autrev.2021.102932.
  • 27. Ramirez MU, Hernandez SR, Soto-Pantoja DR, Cook KL. Endoplasmic reticulum stress pathway, the unfolded protein response, modulates immune function in the tumor microenvironment to impact tumor progression and therapeutic response. Int J Mol Sci. 2019;21(1):169. doi:10.3390/ijms21010169.
  • 28. Shimizu A, Kaira K, Yasuda M, Asao T, Ishikawa O. Clinical and pathological significance of ER stress marker (BiP/GRP78 and PERK) expression in malignant melanoma. Pathol Oncol Res. 2017;23(1):111-116.
  • 29. Shi MH, Wu Y, Li L, Cai YF, Liu M, Gao XH, Chen HD. (2017). Meta‐analysis of the association between vitiligo and the level of superoxide dismutase or malondialdehyde. Clinical and Experimental Dermatology, 42(1), 21-29.
  • 30. Rashighi M, Harris JE. Vitiligo pathogenesis and emerging treatments. Dermatol Clin. 2017;35(2):257-265. doi: 10.1016/j.det.2016.11.014.
  • 31. Malgarin CM, Nosach R, Novakovic P, Suleman M, Ladinig A, Detmer SE, Harding JCS, et al. Classification of fetal resilience to porcine reproductive and respiratory syndrome (PRRS) based on temporal viral load in late gestation maternal tissues and fetuses. Virus Res. 2019;260:151-162. doi:10.1016/j.virusres.2018.12.002.
  • 32. Liu C, Han C, Liu J. The role of toll-like receptors in oncotherapy. Oncol Res. 2019;27(8):965-978. doi:10.3727/096504019x15498329881440.
  • 33. Ryan GE, Harris JE, Richmond JM. Resident memory T cells in autoimmune skin diseases. Front Immunol. 2021;12:652191. doi: 10.3389/fimmu.2021.6521
  • 34. Abdel-Malek ZA, Jordan C, Ho T, Upadhyay PR, Fleischer A, Hamzavi I. The enigma and challenges of vitiligo pathophysiology and treatment. Pigment Cell Melanoma Res. 2020. doi:10.1111/pcmr.12878
  • 35. Xie H, Zhou F, Liu L, Zhu G, Li Q, Li C, Gao T. Vitiligo: How do oxidative strss-induced autoantigens triger autoimmunity? J Dermatol Sci. 2016;81(1):3-9. doi:10.1016/j.jdermsci.2015.09.003.
  • 36. Sherif AS, Enas T. Understanding the role of lymphocytes in vitiligo. Int J Immunol Immunother. 2021;7:060. doi.org/10.23937/2378-3672/1410060.
  • 37. Ruiz-Argüelles A, Brito GJ, Reyes-Izquierdo P, Pérez-Romano B, Sánchez-Sosa S. Apoptosis of melanocytes in vitiligo results from antibody penetration. J Autoimmun. 2017;29(4):281-286. doi:10.1016/j.jaut.2007.07.012.
  • 38. Riding RL, Harris JE. The role of memory CD8+ T cells in vitiligo. J Immunol. 2019;203(1):11-19. doi: 10.4049/jimmunol.1900027.
  • 39. Arora A, Kumaran M. Pathogenesis of vitiligo: An update. Pigment Int. 2017;4(2): 65. doi: 10.4103/2349-5847.219673.