The Role of EREG, PTPN1, and SERPINB7 Genes in the Pathogenesis of Psoriasis: May SERPINB7 Be Protective and a Marker of Severity for Psoriasis?

Citation: Ayvaz HH, Öztürk KH, Seyirci MA, et al. The role of EREG, PTPN1, and SERPINB7 genes in the pathogenesis of psoriasis: May SERPINB7 be protective and a marker of severity for psoriasis?. Dermatol Pract Concept. 2023;13(2):e2023085. DOI: https://doi.org/10.5826/dpc.1302a85

Accepted: September 26, 2022; Published: April 2023

Copyright: ©2023 Ayvaz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.

Funding: None.

Competing interests: None.

Authorship: All authors have contributed significantly to this publication.

Corresponding author: Havva Hilal Ayvaz, Çünür Mah SDÜ Dermatology Department, 32260, Isparta/TURKEY. E-mail: drhhilalayvaz@gmail.com, Phone number: +905309505907

Abstract

Introduction: Psoriasis is a chronic inflammatory dermatological disease with complex pathogenesis in which many immune system cells, including keratinocytes, play a role. Many genes regulate the proliferation of keratinocytes and other immune cells that have essential roles in the pathogenesis of psoriasis.The expressions of EREG, PTPN1, and SERPINB7 genes were shown as upregulated in psoriatic skins in a few studies previously.

Objectives: We aimed to evaluate the expressions of these genes in psoriatic lesional skin and com-pared them with non-lesional adjacent skin of the same patients and normal skin of healthy controls.

Results: Our results revealed that the expressions of EREG and PTPN1 genes were upregulated,whereas the SERPINB7 gene expression was down regulated in the psoriatic skin of the patients than normal skin of controls. Moreover, the expression level of the SERPINB7 gene was also negatively correlated with the severity of the disease among patients.

Conclusions: According to our results, overexpression of EREG and PTPN1 genes, and decreased expression of SERPINB7 gene may lead to the development of psoriasis.

Keywords : psoriasis, epiregulin, tyrosine-protein phosphatase non-receptor type 1, serine proteinase inhibitors

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

References

1. Gudjonsson JE, Ding J, Johnston A, et al. Assessment of the psoriatic transcriptome in a large sample: additional regulated genes and comparisons with in vitro models. J Invest Dermatol. 2010;130(7):1829-1840. 2. Shirakata Y, Kishimoto J, Tokumaru S, et al. Epiregulin, a member of the EGF family, is over-expressed in psoriatic epidermis. J Dermatol Sci. 2007;45(1):69-72. 3. Hashimoto K. Regulation of keratinocyte function by growth factors. J Dermatol Sci 2000;24:46-50. 4. Kubo A, Shiohama A, Sasaki T, et al. Mutations in SERPINB7, encoding a member of the serine protease inhibitor superfamily, cause Nagashima-type palmoplantar keratosis. Am J Hum Genet. 2013;93(5):945-956. 5. AlFadhli S, Al-Zufairi AAM, Nizam R, AlSaffar HA, Al-Mutairi N. De-regulation of diabetic regulatory genes in psoriasis: Deciphering the unsolved riddle. Gene. 2016;593(1):110-116. 6. Cheyssac C, Lecoeur C, Dechaume A, et al. Analysis of common PTPN1 gene variants in type 2 diabetes, obesity and associated phenotypes in the French population. BMC Med Genet. 2006;7:44. 7. Yin X, Lin Y, Shen C, et al. Integration of expression quantitative trait loci and pleiotropy identifies a novel psoriasis susceptibility gene, PTPN1. J Gene Med. 2017;19(1-2):10.1002/jgm.2939. 8. Wang Z, Zheng H, Zhou H, et al. Systematic screening and identification of novel psoriasis‑specific genes from the transcriptome of psoriasis‑like keratinocytes. Mol Med Rep. 2019;19(3):1529-1542. 9. Benezeder T, Painsi C, Patra V, et al. Dithranol targets keratinocytes, their crosstalk with neutrophils and inhibits the IL-36 inflammatory loop in psoriasis. Elife. 2020;9:e56991. 10. Zheng H. SerpinB7 deficiency contributes to development of psoriasis via Calcium-mediated keratinocyte differentiation dysfunction. J Immunol. 2021; 109-111. 11. Langley RG, Ellis CN. Evaluating psoriasis with Psoriasis Area and Severity Index, Psoriasis Global Assessment, and Lattice System Physician's Global Assessment. J Am Acad Dermatol. 2004;51(4):563-569. 12. Ogawa K, Okada Y. The current landscape of psoriasis genetics in 2020. J Dermatol Sci. 2020;99(1):2-8. 13. Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370(9583):263-271. 14. Sagoo GS, Tazi-Ahnini R, Barker JW, et al. Meta-analysis of genome-wide studies of psoriasis susceptibility reveals linkage to chromosomes 6p21 and 4q28-q31 in Caucasian and Chinese Hans population. J Invest Dermatol. 2004;122(6):1401-1405. 15. Pastore S, Mascia F, Mariani V, Girolomoni G. The epidermal growth factor receptor system in skin repair and inflammation. J Invest Dermatol. 2008;128(6):1365-1374. 16. Lu Q, Jiang G. Progress in the application of reflectance confocal microscopy in dermatology. Postepy Dermatol Alergol. 2021;38(5):709-715. 17. Iwata H, Haga N, Ujiie H. Possible role of epiregulin from dermal fibroblasts in the keratinocyte hyperproliferation of psoriasis. J Dermatol. 2021;48(9):1433-1438. 18. Shirasawa S, Sugiyama S, Baba I, et al. Dermatitis due to epiregulin deficiency and a critical role of epiregulin in immune-related responses of keratinocyte and macrophage. Proc Natl Acad Sci U S A. 2004;101(38):13921-13926. 19. Wittmann M, Macdonald A, Renne J. IL-18 and skin inflammation. Autoimmun Rev. 2009;9(1):45-48. 20. Sedimbi SK, Hagglof T, Karlsson MC. IL-18 in inflammatory and autoimmune disease. Cell Mol Life Sci 2013; 70:4795–4808. 21. Combs AP. Recent advances in the discovery of competitive protein tyrosine phosphatase 1B inhibitors for the treatment of diabetes, obesity, and cancer. J Med Chem. 2010;53(6):2333-2344. 22. Kipfer-Coudreau S, Eberlé D, Sahbatou M, et al. Single nucleotide polymorphisms of protein tyrosine phosphatase 1B gene are associated with obesity in morbidly obese French subjects. Diabetologia. 2004;47(7):1278-1284. 23. Bento JL, Palmer ND, Mychaleckyj JC, et al. Association of protein tyrosine phosphatase 1B gene polymorphisms with type 2 diabetes. Diabetes. 2004;53(11):3007-3012. 24. Buerger C, Richter B, Woth K, et al. Interleukin-1β interferes with epidermal homeostasis through induction of insulin resistance: implications for psoriasis pathogenesis. J Invest Dermatol. 2012;132(9):2206-2214. 25. Holm JG, Thomsen SF. Type 2 diabetes and psoriasis: links and risks. Psoriasis (Auckl). 2019;9:1-6. 26. Shiiba M, Nomura H, Shinozuka K, et al. Down-regulated expression of SERPIN genes located on chromosome 18q21 in oral squamous cell carcinomas. Oncol Rep. 2010;24(1):241-249.