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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

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

Author(s): Ruimin Bai, Shaobo Wu, Xinyi Liu, Zixuan Xing, Ruiting Luo, Wen Zhang, Meng Liu, Xinyu Ma, Hao Lei, Ning Wang and Yan Zheng*

Volume 27, Issue 9, 2024

Published on: 03 October, 2023

Page: [1318 - 1328] Pages: 11

DOI: 10.2174/0113862073238968230920054712

Price: $65

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Abstract

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.

Keywords: Psoriasis, autophagy, bioinformatics, GEO, gene ontology (GO), DEGs.

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[1]
Griffiths, C.E.M.; Armstrong, A.W.; Gudjonsson, J.E.; Barker, J.N.W.N. Psoriasis. Lancet, 2021, 397(10281), 1301-1315.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1159/000500470] [PMID: 31269494]
[4]
Wu, D.J.; Adamopoulos, I.E. Autophagy and autoimmunity. Clin. Immunol., 2017, 176, 55-62.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1371/journal.pone.0101937] [PMID: 25010647]
[6]
Boehncke, W.H.; Schön, M.P. Psoriasis. Lancet, 2015, 386(9997), 983-994.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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]

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