Vol 8, No 4 (2022)
Review paper
Published online: 2022-08-08

open access

Page views 4787
Article views/downloads 70
Get Citation

Connect on Social Media

Connect on Social Media

Autophagy in psoriasis and vitiligo

Aleksandra Białczyk1, Rafał Czajkowski2
Forum Dermatologicum 2022;8(4):153-157.

Abstract

Autophagy is a primary catabolic process in eukaryotes which is responsible for degrading dysfunctional and redundant cellular organelles and proteins. The autophagy process plays several roles in maintaining cellular homeostasis, including an endogenous defence mechanism that might play an important role in the development and progression of skin diseases. Psoriasis and vitiligo are common chronic inflammatory skin disorders. Psoriasis is characterized by well-demarcated, erythematous, thickened plaques with an overlying scale. Exact aetiology is complex and influenced by genetic and environmental factors but is not entirely explained. Defects of autophagy in psoriatic skin are likely involved in increased inflammation and disturbed keratinocyte differentiation. Research indicates that autophagy disorders may be associated with various pathways and molecules such as PI3K/AKT/mTOR or toll-like receptors. Vitiligo is characterized by the loss of functional melanocytes. Many hypotheses have been proposed for the pathogenesis of this disease. Autoimmunity and oxidative stress in melanocytes remain the most frequently mentioned. Deregulated autophagy in vitiligo melanocytes might disrupt the antioxidant defence system, which causes melanocytes to have oxidative insults. Still, due to the complexity of this process, its precise role in immune-related inflammatory skin diseases such as psoriasis and vitiligo remains unclear. Objective results will enable the application of new therapeutic strategies.

Article available in PDF format

View PDF Download PDF file

References

  1. Nagar R. Autophagy: A brief overview in perspective of dermatology. Indian J Dermatol Venereol Leprol. 2017; 83(3): 290–297.
  2. Choi MS, Chae YJ, Choi JiW, et al. Potential therapeutic approaches through modulating the autophagy process for skin barrier dysfunction. Int J Mol Sci. 2021; 22(15).
  3. Guo Y, Zhang Xu, Wu T, et al. Autophagy in skin diseases. Dermatology. 2019; 235(5): 380–389.
  4. Yu T, Zuber J, Li J. Targeting autophagy in skin diseases. J Mol Med (Berl). 2015; 93(1): 31–38.
  5. Wu DJ, Adamopoulos IE. Autophagy and autoimmunity. Clin Immunol. 2017; 176: 55–62.
  6. Liu C, Gu L, Ding J, et al. Autophagy in skin barrier and immune-related skin diseases. J Dermatol. 2021; 48(12): 1827–1837.
  7. Li Li, Chen Xu, Gu H. The signaling involved in autophagy machinery in keratinocytes and therapeutic approaches for skin diseases. Oncotarget. 2016; 7(31): 50682–50697.
  8. Yin H, Wu H, Chen Y, et al. The therapeutic and pathogenic role of autophagy in autoimmune diseases. Front Immunol. 2018; 9: 1512.
  9. Lee SH, Jeong SeK, Ahn SKu. An update of the defensive barrier function of skin. Yonsei Med J. 2006; 47(3): 293–306.
  10. Kanda N. Psoriasis: pathogenesis, comorbidities, and therapy updated. Int J Mol Sci. 2021; 22(6).
  11. Griffiths C, Barker J. Pathogenesis and clinical features of psoriasis. The Lancet. 2007; 370(9583): 263–271.
  12. Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis: a review. JAMA. 2020; 323(19): 1945–1960.
  13. Grän F, Kerstan A, Serfling E, et al. Current developments in the immunology of psoriasis. Yale J Biol Med. 2020; 93(1): 97–110.
  14. Douroudis K, Kingo K, Traks T, et al. Polymorphisms in the ATG16L1 gene are associated with psoriasis vulgaris. Acta Derm Venereol. 2012; 92(1): 85–87.
  15. Varshney P, Saini N. PI3K/AKT/mTOR activation and autophagy inhibition plays a key role in increased cholesterol during IL-17A mediated inflammatory response in psoriasis. Biochim Biophys Acta Mol Basis Dis. 2018; 1864(5 Pt A): 1795–1803.
  16. Tang H, Tang X, Guo Ze, et al. AURKA facilitates the psoriasis-related inflammation by impeding autophagy-mediated AIM2 inflammasome suppression. Immunol Lett. 2021; 240: 98–105.
  17. Tang ZL, Zhang K, Lv SC, et al. LncRNA MEG3 suppresses PI3K/AKT/mTOR signalling pathway to enhance autophagy and inhibit inflammation in TNF-α-treated keratinocytes and psoriatic mice. Cytokine. 2021; 148: 155657.
  18. Shen H, Sha Y, Huang J, et al. The roles of AMPK-mediated autophagy and mitochondrial autophagy in a mouse model of imiquimod-induced psoriasis. Am J Transl Res. 2021; 13: 12626–12637.
  19. Nada EA, Muhammad EMS, Ahmed SFM, et al. Assessment of the effect of metabolic syndrome on the autophagy marker LC3 in psoriasis vulgaris patients: a cross-sectional study. Clin Cosmet Investig Dermatol. 2020; 13: 1005–1013.
  20. Wang Z, Zhou H, Zheng H, et al. Autophagy-based unconventional secretion of HMGB1 by keratinocytes plays a pivotal role in psoriatic skin inflammation. Autophagy. 2021; 17(2): 529–552.
  21. Qiu X, Zheng L, Liu X, et al. ULK1 inhibition as a targeted therapeutic strategy for psoriasis by regulating keratinocytes and their crosstalk with neutrophils. Front Immunol. 2021; 12: 714274.
  22. Karabowicz P, Wroński A, Ostrowska H, et al. Reduced proteasome activity and enhanced autophagy in blood cells of psoriatic patients. Int J Mol Sci. 2020; 21(20): 7608.
  23. Amer AS, Samaka RM, Moftah NH. Beclin1 in psoriasis: an immunohistochemical study. Clin Exp Dermatol. 2021; 46(5): 851–860.
  24. Kim HR, Kang SY, Kim HO, et al. Role of aryl hydrocarbon receptor activation and autophagy in psoriasis-related inflammation. Int J Mol Sci. 2020; 21(6): 2195.
  25. Kim JE, Kim HR, Kang SY, et al. Aryl hydrocarbon receptor and autophagy-related protein microtubule-associated protein light chain 3 expression in psoriasis. Ann Dermatol. 2021; 33(2): 138–146.
  26. Li XM, Jung KE, Yim SuH, et al. Autophagy suppresses toll-like receptor 3-mediated inflammatory reaction in human epidermal keratinocytes. Biomed Res Int. 2020; 2020: 4584626.
  27. Lee HM, Shin DM, Yuk JM, et al. Autophagy negatively regulates keratinocyte inflammatory responses via scaffolding protein p62/SQSTM1. J Immunol. 2011; 186(2): 1248–1258.
  28. Yue Lu, Ailin W, Jinwei Z, et al. PSORI-CM02 ameliorates psoriasis in vivo and in vitro by inducing autophagy via inhibition of the PI3K/Akt/mTOR pathway. Phytomedicine. 2019; 64: 153054.
  29. Ezzedine K, Eleftheriadou V, Whitton M, et al. Vitiligo. The Lancet. 2015; 386(9988): 74–84.
  30. Wu X, Yang Y, Xiang L, et al. The fate of melanocyte: Mechanisms of cell death in vitiligo. Pigment Cell Melanoma Res. 2021; 34(2): 256–267.
  31. Qiao Z, Wang X, Xiang L, et al. Dysfunction of autophagy: a possible mechanism involved in the pathogenesis of vitiligo by breaking the redox balance of melanocytes. Oxid Med Cell Longev. 2016: 3401570.
  32. Jeong TJ, Shin MK, Uhm YK, et al. Association of UVRAG polymorphisms with susceptibility to non-segmental vitiligo in a Korean sample. Exp Dermatol. 2010; 19(8): e323–e325.
  33. Sastry KS, Naeem H, Mokrab Y, et al. RNA-seq reveals dysregulation of novel melanocyte genes upon oxidative stress: implications in vitiligo pathogenesis. Oxid Med Cell Longev. 2019; 2019: 2841814.
  34. Yu H, Lin X, Huang Y, et al. The difference in expression of autophagy-related proteins in lesional and perilesional skin in adult patients with active and stable generalized vitiligo-a cross-sectional pilot study. Indian J Dermatol. 2021; 66(4): 331–336.
  35. He Y, Li S, Zhang W, et al. Dysregulated autophagy increased melanocyte sensitivity to HO-induced oxidative stress in vitiligo. Sci Rep. 2017; 7: 42394.
  36. Naguib R, Rashed L. Role of autophagy in nonsegmental vitiligo Naguid and Rashed. Egypt Journal of Dermatol and Venerol. 2021; 41(1): 22.
  37. Elmasry M, El-Hanafy G, Nada H, et al. Expression of the autophagic markers, light chain 3-I, light chain 3-II, and beclin 1, in vitiligo: a case–control study. J Egypt Womens Dermatol Soc. 2021; 18(2): 89.
  38. Kalie E, Razi M, Tooze SA. ULK1 regulates melanin levels in MNT-1 cells independently of mTORC1. PLoS One. 2013; 8(9): e75313.
  39. Zhou J, An X, Dong J, et al. IL-17 induces cellular stress microenvironment of melanocytes to promote autophagic cell apoptosis in vitiligo. FASEB J. 2018; 32(9): 4899–4916.
  40. Qiao Z, Xu Z, Xiao Q, et al. Dysfunction of ATG7-dependent autophagy dysregulates the antioxidant response and contributes to oxidative stress-induced biological impairments in human epidermal melanocytes. Cell Death Discov. 2020; 6: 31.
  41. Zhang CF, Gruber F, Ni C, et al. Suppression of autophagy dysregulates the antioxidant response and causes premature senescence of melanocytes. J Invest Dermatol. 2015; 135(5): 1348–1357.
  42. Murase D, Hachiya A, Takano K, et al. Autophagy has a significant role in determining skin color by regulating melanosome degradation in keratinocytes. J Invest Dermatol. 2013; 133(10): 2416–2424.
  43. Kim JiY, Kim J, Ahn Y, et al. Autophagy induction can regulate skin pigmentation by causing melanosome degradation in keratinocytes and melanocytes. Pigment Cell Melanoma Res. 2020; 33(3): 403–415.
  44. Bastonini E, Kovacs D, Raffa S, et al. A protective role for autophagy in vitiligo. Cell Death Dis. 2021; 12(4): 318.