New Insight in Etiology of Vitiligo, Association of IncRNA and some Immunological Parameters with Expression of Melanin Concentration Hormone and Sirtuin 1 Genes in Generalized and Segmented Vitiligo
DOI:
https://doi.org/10.35516/jmj.v59i5.2756الكلمات المفتاحية:
Vitiligo ، Long non-coding RNAs، sirtuin 1 gene ، melanin-concentrating hormone، interleukinsالملخص
Background: Long non-coding RNAs (LncRNAs) represent a subset of genetic material exceeding 200 base pairs that lack protein-coding capacity, yet possess the unique capability to modulate gene expression. This study was conducted with the purpose of identifying the expression levels of LncRNA SIRT-1, LncRNA MCH, as well as the serum levels of IL-17, IL-33, and IFNγ in individuals with vitiligo. Furthermore, the investigation aimed to explore the potential correlation between long non-coding RNA and the parameters of study.
Methods: The investigation was carried out on a cohort consisting of 30 patients with Generalized Vitiligo (GV) - both treated and untreated, 30 patients with Segmented Vitiligo (SV) - also both treated and untreated, and 25 Healthy Controls (HC). Using ELISA, the serum levels of IL-17, IL-33, IFNγ, SIRT 1, and PMCH were measured. Additionally, a gene expression analysis of long non-coding RNA (LncRNA) SIRT-1 and LncRNA PMCH was conducted in patients with GV and SV in order to shed light on their potential implications in the pathogenesis of vitiligo.
Results: LncRNA SIRT-1 expression was significantly higher in GV compared to SV (p=0.030, Mann-Whitney test), with mean expression levels of 2.851 (SE: 1.052) and 0.507 (SE: 0.134), respectively. In contrast, no significant difference in LncRNA MCH expression was observed between the two vitiligo types.
Conclusion: After investigation of the association between lncRNA expression of the SIRT1 and MCH genes and their corresponding serum concentrations in vitiligo patients, this research elucidated the dysregulated manifestations of LncRNA SIRT-1 and LncRNA MCH in individuals diagnosed with vitiligo, indicating their potential contributions to the etiology of vitiligo. This mechanism could involve the down regulation of serum SIRT-1 and MCH, as well as the elevation of cytokines. `
المراجع
R. R. Joge, P. U. Kathane, and S. H. Joshi, “Vitiligo: A Narrative Review,” Cureus, vol. 14, no. 9, 2022.
S. L. Said Fernandez et al., “Novel immunological and genetic factors associated with vitiligo: A review,” Exp. Ther. Med., vol. 21, no. 4, p. 1, 2021.
R. Speeckaert, J. Lambert, V. Bulat, A. Belpaire, M. Speeckaert, and N. van Geel, “Autoimmunity in segmental vitiligo,” Front. Immunol., vol. 11, p. 568447, 2020.
[4] M. Alhelf, L. A. Rashed, N. Ragab, and M. F. Elmasry, “Association between long noncoding RNA taurine‐upregulated gene 1 and microRNA‐377 in vitiligo.” Wiley Online Library, 2022.
J. S. Mattick et al., “Long non-coding RNAs: definitions, functions, challenges and recommendations,” Nat. Rev. Mol. Cell Biol., vol. 24, no. 6, pp. 430–447, 2023.
Z. Lou et al., “LncRNA Sirt1-AS upregulates Sirt1 to attenuate aging related deep venous thrombosis,” Aging (Albany NY), vol. 13, no. 5, p. 6918, 2021.
T. R. Mercer, M. E. Dinger, and J. S. Mattick, “Long non-coding RNAs: insights into functions,” Nat. Rev. Genet., vol. 10, no. 3, pp. 155–159, 2009.
E. Prida et al., “Crosstalk between Melanin Concentrating Hormone and Endocrine Factors: Implications for Obesity,” Int. J. Mol. Sci., vol. 23, no. 5, p. 2436, 2022.
R. Madelaine, K. J. Ngo, G. Skariah, and P. Mourrain, “Genetic deciphering of the antagonistic activities of the melanin-concentrating hormone and melanocortin pathways in skin pigmentation,” PLoS Genet., vol. 16, no. 12, p. e1009244, 2020.
Y. Yang et al., “Regulation of SIRT1 and its roles in inflammation,” Front. Immunol., vol. 13, p. 831168, 2022.
A. El-karim, R. Gamal, M. Y. Abdel-Mawla, A.-S. M. Ibrahim, and N. Khalifa, “Serum level of IL-33 in vitiligo,” Zagazig Univ. Med. J., vol. 29, no. 1.2, pp. 149–154, 2023.
P. Custurone et al., “Role of cytokines in vitiligo: pathogenesis and possible targets for old and new treatments,” Int. J. Mol. Sci., vol. 22, no. 21, p. 11429, 2021.
A. Hatice and M. Gönül, “Increased risk of metabolic syndrome in patients with vitiligo,” Balkan Med. J., vol. 34, no. 3, pp. 219–225, 2017.
[14] E. Karagün and S. Baysak, “Levels of TNF-α, IL-6, IL-17, IL-37 cytokines in patients with active vitiligo,” Aging Male, vol. 23, no. 5, pp. 1487–1492, 2020.
L. Zhou et al., “Increased circulating Th17 cells and elevated serum levels of TGF‐beta and IL‐21 are correlated with human non‐segmental vitiligo development,” Pigment Cell Melanoma Res., vol. 28, no. 3, pp. 324–329, 2015.
Y. Zhen, L. Yao, S. Zhong, Y. Song, Y. Cui, and S. Li, “Enhanced Th1 and Th17 responses in peripheral blood in active non-segmental vitiligo,” Arch. Dermatol. Res., vol. 308, pp. 703–710, 2016.
S. Sushama, N. Dixit, R. K. Gautam, P. Arora, A. Khurana, and A. Anubhuti, “Cytokine profile (IL‐2, IL‐6, IL‐17, IL‐22, and TNF‐α) in vitiligo—new insight into pathogenesis of disease,” J. Cosmet. Dermatol., vol. 18, no. 1, pp. 337–341, 2019.
I. A. Gomes et al., “The role of interleukins in vitiligo: a systematic review,” J. Eur. Acad. Dermatology Venereol., vol. 32, no. 12, pp. 2097–2111, 2018.
M. Becatti et al., “SIRT 1 regulates MAPK pathways in vitiligo skin: insight into the molecular pathways of cell survival,” J. Cell. Mol. Med., vol. 18, no. 3, pp. 514–529, 2014.
T. Zhou, D. Li, Y. Deng, and L. Guo, “Update on the role of noncoding RNAs in vitiligo,” Chin. Med. J. (Engl)., vol. 135, no. 7, pp. 793–795, 2022, doi: 10.1097/CM9.0000000000001900.
S. Zhang et al., “Expression patterns of long non-coding RNAs in peripheral blood mononuclear cells of non-segmental vitiligo,” Med. (United States), vol. 100, no. 51, pp. 1–8, 2021, doi: 10.1097/MD.0000000000028399.
E. H. Kemp and A. P. Weetman, “Melanin-concentrating hormone and melanin-concentrating hormone receptors in mammalian skin physiopathology,” Peptides, vol. 30, no. 11, pp. 2071–2075, 2009.
R. W. Doss, A. A. Elrifaie, N. M. Mamdouh, and D. Sabry, “Expression of long noncoding RNA in skin exosomes of patients with vitiligo,” J. Egypt. Women’s Dermatologic Soc., vol. 17, no. 3, pp. 158–163, 2020,
doi: 10.4103/JEWD.JEWD_31_20.
O. KURU, N. SOLAK TEKİN, Ü. ÖZEL TÜRKCÜ, S. KARAKAŞ ÇELİK, and T. EDGÜNLÜ, “SIRT1 Gene Polymorphisms and the Risk of Vitiligo: Molecular Association and in Silico Approach,” Batı Karadeniz Tıp Derg., vol. 7, no. 1, pp. 1–8, 2023, doi: 10.29058/mjwbs.1223300.
S. Zhou et al., “Epigenetic regulation of melanogenesis,” Ageing Res. Rev., vol. 69, p. 101349, 2021.

