Bioinformatic Analysis to Identify and Cellular Experiments to Validate Autophagy-related Genes in Psoriasis


Citar

Texto integral

Resumo

Purpose:To explore differentially expressed genes (DEGs) associated with autophagy in psoriasis using bioinformatics analysis and verify them in an M5-induced psoriatic cell model.

Methods:We obtained gene expression microarray data from patients with psoriasis and normal skin tissues from the dataset GSE78097 of the NCBI Gene Expression Omnibus (GEO) database. R software was used to identify DEGs associated with autophagy in psoriasis. Proteinprotein interaction (PPI) and correlation analyses were used to show interactions between certain genes. Their potential biological roles were determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, all the DEGs associated with autophagy in psoriasis were validated in a psoriatic cell model by RT-qPCR.

Results:28 DEGs associated with autophagy were identified. These genes were linked to one another, and the most connected hub gene was VEGFA, according to PPI analysis. GO and KEGG enrichment analyses revealed various biological pathways associated with autophagy. The RT-qPCR findings of the expression of 18 genes in the psoriatic cell model confirmed the bioinformatics analysis results. The five genes with the most significant differences were IL24, CCL2, NAMPT, PPP1R15A, and SPHK1.

Conclusion:We identified DEGs associated with autophagy in patients with psoriasis. IL24, CCL2, NAMPT, PPP1R15A, and SPHK1 were identified as important genes that may influence psoriasis development through the regulation of autophagy.

Sobre autores

Ruimin Bai

Department of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong University

Email: info@benthamscience.net

Shaobo Wu

Department of Medicine, Xi’an Jiaotong University

Email: info@benthamscience.net

Xinyi Liu

Department of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong University

Email: info@benthamscience.net

Zixuan Xing

Department of Medicine, Xi’an Jiaotong University

Email: info@benthamscience.net

Ruiting Luo

Department of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong University

Email: info@benthamscience.net

Wen Zhang

Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University

Email: info@benthamscience.net

Meng Liu

Department of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong University

Email: info@benthamscience.net

Xinyu Ma

Department of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong University

Email: info@benthamscience.net

Hao Lei

Department of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong University

Email: info@benthamscience.net

Ning Wang

Department of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong University

Email: info@benthamscience.net

Yan Zheng

Department of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong University

Autor responsável pela correspondência
Email: info@benthamscience.net

Bibliografia

  1. Griffiths, C.E.M.; Armstrong, A.W.; Gudjonsson, J.E.; Barker, J.N.W.N. Psoriasis. Lancet, 2021, 397(10281), 1301-1315. doi: 10.1016/S0140-6736(20)32549-6 PMID: 33812489
  2. Griffiths, C.E.M.; Barker, J.N.W.N. Pathogenesis and clinical features of psoriasis. Lancet, 2007, 370(9583), 263-271. doi: 10.1016/S0140-6736(07)61128-3 PMID: 17658397
  3. Guo, Y.; Zhang, X.; Wu, T.; Hu, X.; Su, J.; Chen, X. Autophagy in skin diseases. Dermatology, 2019, 235(5), 380-389. doi: 10.1159/000500470 PMID: 31269494
  4. Wu, D.J.; Adamopoulos, I.E. Autophagy and autoimmunity. Clin. Immunol., 2017, 176, 55-62. doi: 10.1016/j.clim.2017.01.007 PMID: 28095319
  5. Rabeony, H.; Petit-Paris, I.; Garnier, J.; Barrault, C.; Pedretti, N.; Guilloteau, K.; Jegou, J.F.; Guillet, G.; Huguier, V.; Lecron, J.C.; Bernard, F.X.; Morel, F. Inhibition of keratinocyte differentiation by the synergistic effect of IL-17A, IL-22, IL-1α, TNFα and oncostatin M. PLoS One, 2014, 9(7), e101937. doi: 10.1371/journal.pone.0101937 PMID: 25010647
  6. Boehncke, W.H.; Schön, M.P. Psoriasis. Lancet, 2015, 386(9997), 983-994. doi: 10.1016/S0140-6736(14)61909-7 PMID: 26025581
  7. Takahashi, H.; Manabe, A.; Ishida-Yamamoto, A.; Hashimoto, Y.; Iizuka, H. Aberrant expression of apoptosis-related molecules in psoriatic epidermis. J. Dermatol. Sci., 2002, 28(3), 187-197. doi: 10.1016/S0923-1811(01)00162-1 PMID: 11912006
  8. Maiuri, M.C.; Zalckvar, E.; Kimchi, A.; Kroemer, G. Self-eating and self-killing: Crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol., 2007, 8(9), 741-752. doi: 10.1038/nrm2239 PMID: 17717517
  9. Hailfinger, S.; Schulze-Osthoff, K. Impaired autophagy in psoriasis and atopic dermatitis: A new therapeutic target? J. Invest. Dermatol., 2021, 141(12), 2775-2777. doi: 10.1016/j.jid.2021.06.006 PMID: 34565564
  10. Lee, H.M.; Shin, D.M.; Yuk, J.M.; Shi, G.; Choi, D.K.; Lee, S.H.; Huang, S.M.; Kim, J.M.; Kim, C.D.; Lee, J.H.; Jo, E.K. Autophagy negatively regulates keratinocyte inflammatory responses via scaffolding protein p62/SQSTM1. J. Immunol., 2011, 186(2), 1248-1258. doi: 10.4049/jimmunol.1001954 PMID: 21160040
  11. 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), 1795-1803. doi: 10.1016/j.bbadis.2018.02.003 PMID: 29432814
  12. Klapan, K.; Simon, D.; Karaulov, A.; Gomzikova, M.; Rizvanov, A.; Yousefi, S.; Simon, H.U. Autophagy and Skin Diseases. Front. Pharmacol., 2022, 13, 844756. doi: 10.3389/fphar.2022.844756 PMID: 35370701
  13. Mizushima, N.; Kuma, A.; Kobayashi, Y.; Yamamoto, A.; Matsubae, M.; Takao, T.; Natsume, T.; Ohsumi, Y.; Yoshimori, T. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate. J. Cell Sci., 2003, 116(9), 1679-1688. doi: 10.1242/jcs.00381 PMID: 12665549
  14. Douroudis, K.; Kingo, K.; Traks, T.; Reimann, E.; Raud, K.; Rätsep, R.; Mössner, R.; Silm, H.; Vasar, E.; Kõks, S. Polymorphisms in the ATG16L1 gene are associated with psoriasis vulgaris. Acta Derm. Venereol., 2012, 92(1), 85-87. doi: 10.2340/00015555-1183 PMID: 21879234
  15. Feng, L.; Song, P.; Xu, F.; Xu, L.; Shao, F.; Guo, M.; Huang, W.; Kong, L.; Wu, X.; Xu, Q. cis-Khellactone inhibited the proinflammatory macrophages via promoting autophagy to ameliorate imiquimod-induced psoriasis. J. Invest. Dermatol., 2019, 139(9), 1946-1956.e3. doi: 10.1016/j.jid.2019.02.021 PMID: 30878677
  16. Qi, Y.; Zhou, X.; Zhang, H. Autophagy and immunological aberrations in systemic lupus erythematosus. Eur. J. Immunol., 2019, 49(4), 523-533. doi: 10.1002/eji.201847679 PMID: 30776086
  17. Wan, Q.; Jin, L.; Su, Y.; liu, Y.; Li, C.; Wang, Z. Development and validation of autophagy‐related‐gene biomarker and nomogram for predicting the survival of cutaneous melanoma. IUBMB Life, 2020, 72(7), 1364-1378. doi: 10.1002/iub.2258 PMID: 32080971
  18. George, D.M.; Breinlinger, E.C.; Friedman, M.; Zhang, Y.; Wang, J.; Argiriadi, M.; Bansal-Pakala, P.; Barth, M.; Duignan, D.B.; Honore, P.; Lang, Q.; Mittelstadt, S.; Potin, D.; Rundell, L.; Edmunds, J.J. Discovery of selective and orally bioavailable protein kinase Cθ (PKCθ) inhibitors from a fragment hit. J. Med. Chem., 2015, 58(1), 222-236. doi: 10.1021/jm500669m PMID: 25000588
  19. Galimova, E.; Rätsep, R.; Traks, T.; Kingo, K.; Escott-Price, V.; Kõks, S. Interleukin-10 family cytokines pathway: Genetic variants and psoriasis. Br. J. Dermatol., 2017, 176(6), 1577-1587. doi: 10.1111/bjd.15363 PMID: 28150860
  20. Tsai, Y.C.; Tsai, T.F. Anti-interleukin and interleukin therapies for psoriasis: Current evidence and clinical usefulness. Ther. Adv. Musculoskelet. Dis., 2017, 9(11), 277-294. doi: 10.1177/1759720X17735756 PMID: 29344110
  21. Kantaputra, P.; Chaowattanapanit, S.; Kiratikanon, S.; Chaiwarith, R.; Choonhakarn, C.; Intachai, W.; Quarto, N.; Tongsima, S.; Ketudat Cairns, J.R.; Ngamphiw, C.; McGrath, J.A.; Chuamanochan, M. SERPINA1, generalized pustular psoriasis, and adult‐onset immunodeficiency. J. Dermatol., 2021, 48(10), 1597-1601. doi: 10.1111/1346-8138.16081 PMID: 34390020
  22. Gravina, G.; Wasén, C.; Garcia-Bonete, M.J.; Turkkila, M.; Erlandsson, M.C.; Töyrä Silfverswärd, S.; Brisslert, M.; Pullerits, R.; Andersson, K.M.; Katona, G.; Bokarewa, M.I. Survivin in autoimmune diseases. Autoimmun. Rev., 2017, 16(8), 845-855. doi: 10.1016/j.autrev.2017.05.016 PMID: 28564620
  23. Koçak, M.; Bozdoǧan, Ö.; Erkek, E.; Atasoy, P.; Birol, A. Examination of Bcl-2, Bcl-X and bax protein expression in psoriasis. Int. J. Dermatol., 2003, 42(10), 789-793. doi: 10.1046/j.1365-4362.2003.01821.x PMID: 14521691
  24. Wang, B.; Han, D.; Li, F.; Hou, W.; Wang, L.; Meng, L.; Mou, K.; Lu, S.; Zhu, W.; Zhou, Y. Elevated IL-22 in psoriasis plays an anti-apoptotic role in keratinocytes through mediating Bcl-xL/Bax. Apoptosis, 2020, 25(9-10), 663-673. doi: 10.1007/s10495-020-01623-3 PMID: 32632545
  25. Fetter, T.; Niebel, D.; Braegelmann, C.; Wenzel, J. Skin-Associated B cells in the pathogenesis of cutaneous autoimmune diseases—implications for therapeutic approaches. Cells, 2020, 9(12), 2627. doi: 10.3390/cells9122627 PMID: 33297481
  26. Mercurio, L.; Morelli, M.; Scarponi, C.; Scaglione, G.L.; Pallotta, S.; Avitabile, D.; Albanesi, C.; Madonna, S. Enhanced NAMPT-Mediated NAD salvage pathway contributes to psoriasis pathogenesis by amplifying epithelial auto-inflammatory circuits. Int. J. Mol. Sci., 2021, 22(13), 6860. doi: 10.3390/ijms22136860 PMID: 34202251
  27. Shin, S.; Cho, K.; Hahn, S.; Lee, Y.; Kim, Y.; Woo, S.; Ryu, K.; Park, W.; Park, J. Inhibiting sphingosine kinase 2 derived-sphingosine-1-phosphate ameliorates psoriasis-like skin disease via blocking th17 differentiation of naïve CD4 T lymphocytes in mice. Acta Derm. Venereol., 2019, 99(6), 594-601. doi: 10.2340/00015555-3160 PMID: 30834454
  28. Aira, L.E.; Gonçalves, D.; Bossowski, J.P.; Rubio-Patiño, C.; Chiche, J.; Paul-Bellon, R.; Mondragón, L.; Gesson, M.; Lecucq-Ottavi, P.; Obba, S.; Colosetti, P.; Luciano, F.; Bailly-Maitre, B.; Boyer, L.; Jacquel, A.; Robert, G.; Ricci, J.E.; Ortonne, J.P.; Passeron, T.; Lacour, J.P.; Auberger, P.; Marchetti, S. Caspase 1/11 deficiency or pharmacological inhibition mitigates psoriasis-like phenotype in mice. J. Invest. Dermatol., 2019, 139(6), 1306-1317. doi: 10.1016/j.jid.2018.11.031 PMID: 30571969
  29. Tang, H.; Tang, X.; Guo, Z.; Cheng, H.; Zheng, X.; Chen, G.; Huang, H.; Wang, W.; Gao, J.; Sheng, Y.; Fan, X.; Sun, L. AURKA facilitates the psoriasis-related inflammation by impeding autophagy-mediated AIM2 inflammasome suppression. Immunol. Lett., 2021, 240, 98-105. doi: 10.1016/j.imlet.2021.10.004 PMID: 34710506
  30. Behfar, S.; Hassanshahi, G.; Nazari, A.; Khorramdelazad, H. A brief look at the role of monocyte chemoattractant protein-1 (CCL2) in the pathophysiology of psoriasis. Cytokine, 2018, 110, 226-231. doi: 10.1016/j.cyto.2017.12.010 PMID: 29277337
  31. Batinac, T.; Zamolo, G.; Hadzisejdić, I.; Zauhar, G.; Brumini, G.; Ruzić, A.; Persić, V. Expression of Bcl-2 family proteins in psoriasis. Croat. Med. J., 2007, 48(3), 319-326. PMID: 17589974
  32. Li, W.; Man, X.Y.; Chen, J.Q.; Zhou, J.; Cai, S.Q.; Zheng, M. Targeting VEGF/VEGFR in the treatment of psoriasis. Discov. Med., 2014, 18(98), 97-104. PMID: 25227750

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML

Declaração de direitos autorais © Bentham Science Publishers, 2024