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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

The MAP2K2 Gene as Potential Diagnostic Marker in Monitoring Adalimumab Therapy of Psoriatic Arthritis

Author(s): Agata Krawczyk, Barbara Strzałka-Mrozik*, Karol Juszczyk, Magdalena Kimsa-Dudek, Dominika Wcisło-Dziadecka and Joanna Gola

Volume 24, Issue 2, 2023

Published on: 18 August, 2022

Page: [330 - 340] Pages: 11

DOI: 10.2174/1389201023666220628111644

Price: $65

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Abstract

Background: MAP kinases are some of the cascades that are specialized in the cell’s response to external stimuli. Their impaired functioning can be observed during the course of psoriatic arthritis. Currently, the best-known class of biological drugs is the inhibitors of the proinflammatory cytokine TNF-α, including adalimumab.

Objective: The aim of this study was to assess changes in the expression of MAP kinase genes in patients with psoriatic arthritis treated with adalimumab, as well as to determine which of the analyzed transcripts could be used as a diagnostic or therapeutic target.

Methods: An analysis was performed on the total RNA extracted from PBMCs of patients with psoriatic arthritis before and after three months of adalimumab therapy as well as from a control group. Changes in the expression of the mitogen-activated protein kinase genes were assessed using the HG-U133A 2.0 oligonucleotide microarray method, while the obtained results were validated using the real-time RT-qPCR method.

Results: Using the oligonucleotide microarray method, 14 genes coded for proteins from the MAPK group were identified with at least a two-fold change of expression in the control group and during adalimumab therapy. Validation of the results confirmed a statistically significant decrease in the transcriptional activity of the MAP2K2 gene in the group of patients three months after the administration of adalimumab relative to the control group.

Conclusion: Adalimumab therapy alters the expression of MAPK-coding genes. The assessment of the number of MAP2K2 mRNA molecules can potentially be used in diagnostic analyses or in monitoring adalimumab therapy.

Keywords: MAPK, MAPK2, gene expression, psoriatic arthritis, adalimumab, anti-TNF.

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[1]
Nadal-Ribelles, M.; Sole, C.; Martinez-Cebrian, G.; Posas, F.; de Nadal, E. Shaping the Transcriptional Landscape through MAPK Signaling; IntechOpen, 2018, pp. 1-22.
[2]
Lee, S.; Rauch, J.; Kolch, W. Targering MAPK signaling in cancer: Mechanism of drug resistance and sensitivity. Int. J. Mol. Sci., 2020, 21, 1102.
[http://dx.doi.org/10.3390/ijms21031102]
[3]
Yue, J.; López, J.M. Understanding MAPK signaling pathways in apoptosis. Int. J. Mol. Sci., 2020, 21(7), 2346.
[http://dx.doi.org/10.3390/ijms21072346] [PMID: 32231094]
[4]
Roskoski, R. Jr Targeting ERK1/2 protein-serine/threonine kinases in human cancers. Pharmacol. Res., 2019, 142, 151-168.
[http://dx.doi.org/10.1016/j.phrs.2019.01.039] [PMID: 30794926]
[5]
Zhao, C.; Wang, P.; Si, T.; Hsu, C.C.; Wang, L.; Zayed, O.; Yu, Z.; Zhu, Y.; Dong, J.; Tao, W.A.; Zhu, J.K. MAP kinase cascades regulate the cold response by modulating ICE1 protein stability. Dev. Cell, 2017, 43(5), 618-629.e5.
[http://dx.doi.org/10.1016/j.devcel.2017.09.024] [PMID: 29056551]
[6]
Bequette, C.J.; Hind, S.R.; Pulliam, S.; Higgins, R.; Stratmann, J.W. MAP kinases associate with high molecular weight multiprotein complexes. J. Exp. Bot., 2018, 69(3), 643-654.
[http://dx.doi.org/10.1093/jxb/erx424] [PMID: 29240956]
[7]
Sabio, G.; Davis, R.J. TNF and MAP kinase signalling pathways. Semin. Immunol., 2014, 26(3), 237-245.
[http://dx.doi.org/10.1016/j.smim.2014.02.009] [PMID: 24647229]
[8]
Sinkala, M.; Nkhoma, P.; Mulder, N.; Martin, D.P. Integrated molecular characterisation of the MAPK pathways in human cancers reveals pharmacologically vulnerable mutations and gene dependencies. Commun. Biol., 2021, 4(1), 9.
[http://dx.doi.org/10.1038/s42003-020-01552-6] [PMID: 33398072]
[9]
Zaidi, I.; Ebel, C.; Belgaroui, N.; Ghorbel, M.; Amara, I.; Hanin, M. The wheat MAP kinase phosphatase 1 alleviates salt stress and increases antioxidant activities in Arabidopsis. J. Plant Physiol., 2016, 193, 12-21.
[http://dx.doi.org/10.1016/j.jplph.2016.01.011] [PMID: 26927025]
[10]
Shah, S.Z.A.; Zhao, D.; Hussain, T.; Yang, L. The role of unfolded protein response and mitogen-activated protein kinase signaling in neurodegenerative diseases with special focus on prion diseases. Front. Aging Neurosci., 2017, 9, 120.
[http://dx.doi.org/10.3389/fnagi.2017.00120] [PMID: 28507517]
[11]
Lee, S.; Youn, K.; Jun, M. Major compounds of red ginseng oil attenuate Aβ25-35-induced neuronal apoptosis and inflammation by modulating MAPK/NF-κB pathway. Food Funct., 2018, 9(8), 4122-4134.
[http://dx.doi.org/10.1039/C8FO00795K] [PMID: 30014084]
[12]
Tong, H.; Zhang, X.; Meng, X.; Lu, L.; Mai, D.; Qu, S. Simvastatin inhibits activation of NADPH Oxidase/p38 MAPK pathway and enhances expression of antioxidant protein in parkinson disease models. Front. Mol. Neurosci., 2018, 11, 165.
[http://dx.doi.org/10.3389/fnmol.2018.00165] [PMID: 29872377]
[13]
Egu, D.T.; Walter, E.; Spindler, V.; Waschke, J. Inhibition of p38MAPK signalling prevents epidermal blistering and alterations of desmosome structure induced by pemphigus autoantibodies in human epidermis. Br. J. Dermatol., 2017, 177(6), 1612-1618.
[http://dx.doi.org/10.1111/bjd.15721] [PMID: 28600798]
[14]
Bowcock, A.M.; Shannon, W.; Du, F.; Duncan, J.; Cao, K.; Aftergut, K.; Catier, J.; Fernandez-Vina, M.A.; Menter, A. Insights into psoriasis and other inflammatory diseases from large-scale gene expression studies. Hum. Mol. Genet., 2001, 10(17), 1793-1805.
[http://dx.doi.org/10.1093/hmg/10.17.1793] [PMID: 11532989]
[15]
Ocampo, V.; Gladman, D. Psoriatic arthritis. F1000 Research, 2019, 8, 1-16.
[16]
Ma, J.; Liang, N.; Chen, J.; Bai, Y. The association between biologic agents and the risk of cardiovascular events in patients with psoriasis and psoriatic arthritis: A protocol for a systematic review and meta-analysis. Medicine, (Baltimore), 2019, 98(47), e18063.
[http://dx.doi.org/10.1097/MD.0000000000018063] [PMID: 31764836]
[17]
Lories, R.J.; Derese, I.; Luyten, F.P.; de Vlam, K. Activation of nuclear factor kappa B and mitogen activated protein kinases in psoriatic arthritis before and after etanercept treatment. Clin. Exp. Rheumatol., 2008, 26(1), 96-102.
[PMID: 18328153]
[18]
Tsanov, K.M.; Pearson, D.S.; Wu, Z.; Han, A.; Triboulet, R.; Seligson, M.T.; Powers, J.T.; Osborne, J.K.; Kane, S.; Gygi, S.P.; Gregory, R.I.; Daley, G.Q. LIN28 phosphorylation by MAPK/ERK couples signalling to the post-transcriptional control of pluripotency. Nat. Cell Biol., 2017, 19(1), 60-67.
[http://dx.doi.org/10.1038/ncb3453] [PMID: 27992407]
[19]
Arthur, J.S.; Ley, S.C. Mitogen-activated protein kinases in innate immunity. Nat. Rev. Immunol., 2013, 13(9), 679-692.
[http://dx.doi.org/10.1038/nri3495] [PMID: 23954936]
[20]
Mavropoulos, A.; Rigopoulou, E.I.; Liaskos, C.; Bogdanos, D.P.; Sakkas, L.I. The role of p38 MAPK in the aetiopathogenesis of psoriasis and psoriatic arthritis. Clin. Dev. Immunol., 2013, 2013, 569751.
[http://dx.doi.org/10.1155/2013/569751] [PMID: 24151518]
[21]
Zangrilli, A.; Bavetta, M.; Bianchi, L. Adalimumab in children and adolescents with severe plaque psoriasis: A safety evaluation. Expert Opin. Drug Saf., 2020, 19(4), 433-438.
[http://dx.doi.org/10.1080/14740338.2020.1752659] [PMID: 32250180]
[22]
Nassar-Sheikh Rashid, A.; Schonenberg-Meinema, D.; Bergkamp, S.C.; Bakhlakh, S.; de Vries, A.; Rispens, T.; Kuijpers, T.W.; Wolbink, G.; van den Berg, J.M. Therapeutic drug monitoring of anti-TNF drugs: An overview of applicability in daily clinical practice in the era of treatment with biologics in Juvenile Idiopathic Arthritis (JIA). Pediatr. Rheumatol. Online J., 2021, 19(1), 59.
[http://dx.doi.org/10.1186/s12969-021-00545-x] [PMID: 33926495]
[23]
McGagh, D.; Coates, L.C. Assessment of the many faces of PsA: Single and composite measures in PsA clinical trials. Rheumatology, (Oxford), 2020, 59(Suppl. 1), i29-i36.
[http://dx.doi.org/10.1093/rheumatology/kez305] [PMID: 32159792]
[24]
Szepietowski, J.; Adamski, Z.; Chodorowska, G.; Gliński, W.; Kaszuba, A.; Placek, W.; Rudnicka, L.; Reich, A. Guidelines of Polish dermatological Society on the treatment of psoriasis vulgaris and arthropathic psoriasis (psoriatic arthritis) with biological drugs. Dermatol. Rep., 2010, 97, 1-3.
[25]
Wcisło-Dziadecka, D.; Grabarek, B.; Kruszniewska-Rajs, C.; Swinarew, A.; Jasik, K.; Rozwadowska, B.; Krawczyk, A. Analysis of molecular and clinical parameters of 4-year adalimumab therapy in psoriatic patients. Postepy Dermatol. Alergol., 2020, 37(5), 736-745.
[http://dx.doi.org/10.5114/ada.2020.100484] [PMID: 33240014]
[26]
Wcisło-Dziadecka, D.L.; Grabarek, B.; Kruszniewska-Rajs, C.; Gola, J.M.; Simka, K.; Mazurek, U. Analysis of the clinical response and changes in the expression of TNF-α and its TNFR1 and TNFR2 receptors in patients with psoriasis vulgaris treated with ustekinumab. Adv. Clin. Exp. Med., 2020, 29(2), 235-241.
[http://dx.doi.org/10.17219/acem/112607] [PMID: 32125100]
[27]
Duarte, A.; Mebrahtu, T.; Goncalves, P.S.; Harden, M.; Murphy, R.; Palmer, S.; Woolacott, N.; Rodgers, M.; Rothery, C. Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people: Systematic review and economic evaluation. Health Technol. Assess., 2017, 21(64), 1-244.
[http://dx.doi.org/10.3310/hta21640] [PMID: 29105621]
[28]
Akash, M.S.H.; Rehman, K.; Liaqat, A. Tumor necrosis factor-alpha: Role in development of insulin resistance and pathogenesis of type 2 diabetes mellitus. J. Cell. Biochem., 2018, 119(1), 105-110.
[http://dx.doi.org/10.1002/jcb.26174] [PMID: 28569437]
[29]
Hohenberger, M.; Cardwell, L.A.; Oussedik, E.; Feldman, S.R. Interleukin-17 inhibition: Role in psoriasis and inflammatory bowel disease. J. Dermatolog. Treat., 2018, 29(1), 13-18.
[http://dx.doi.org/10.1080/09546634.2017.1329511] [PMID: 28521565]
[30]
Lendak, D.F.; Mihajlović, D.M.; Novakov-Mikić, A.S.; Mitić, I.M.; Boban, J.M.; Brkić, S.V. The role of TNF-α superfamily members in immunopathogenesis of sepsis. Cytokine, 2018, 111, 125-130.
[http://dx.doi.org/10.1016/j.cyto.2018.08.015]
[31]
Tripathi, R.; Liu, Z.; Jain, A.; Lyon, A.; Meeks, C.; Richards, D.; Liu, J.; He, D.; Wang, C.; Nespi, M.; Rymar, A.; Wang, P.; Wilson, M.; Plattner, R. Combating acquired resistance to MAPK inhibitors in melanoma by targeting Abl1/2-mediated reactivation of MEK/ERK/MYC signaling. Nat. Commun., 2020, 11(1), 5463.
[http://dx.doi.org/10.1038/s41467-020-19075-3] [PMID: 33122628]
[32]
Kaya, Y.; Yildiz, A. Post-translational regulation of the activity of ERK/MAPK and PI3K/AKT signaling pathways in neuroblastoma cancer. Life Sci., 2021.
[http://dx.doi.org/10.5772/intechopen.96176]
[33]
Tariq, S.; Alam, O.; Amir, M. Synthesis, anti-inflammatory, p38α MAP kinase inhibitory activities and molecular docking studies of quinoxaline derivatives containing triazole moiety. Bioorg. Chem., 2018, 76, 343-358.
[http://dx.doi.org/10.1016/j.bioorg.2017.12.003] [PMID: 29227918]
[34]
Krawczyk, A.; Strzałka-Mrozik, B.; Grabarek, B.; Wcisło-Dziadecka, D.; Kimsa-Dudek, M.; Kruszniewska-Rajs, C.; Gola, J. mRNA level of ROCK1, RHOA, and LIMK2 as genes associated with apoptosis in evaluation of effectiveness of adalimumab treatment. Pharmacol. Rep., 2020, 72(2), 389-399.
[http://dx.doi.org/10.1007/s43440-020-00068-4] [PMID: 32124389]
[35]
Tan, Y.; Qi, Q.; Lu, C.; Niu, X.; Bai, Y.; Jiang, C.; Wang, Y.; Zhou, Y.; Lu, A.; Xiao, C. Cytokine imbalance as common mechanism in both psoriasis and rheumatoid arthritis. Mediat. Inflamm., 2017.
[http://dx.doi.org/10.1155/2017/2405291]
[36]
Lamot, L.; Borovecki, F.; Tambic Bukovac, L.; Vidovic, M.; Perica, M.; Gotovac, K.; Harjacek, M. Aberrant expression of shared master-key genes contributes to the immunopathogenesis in patients with juvenile spondyloarthritis. PLoS One, 2014, 9(12), e115416.
[http://dx.doi.org/10.1371/journal.pone.0115416] [PMID: 25506924]
[37]
Ganesan, R.; Doss, H.M.; Rasool, M. Majoon ushba, a polyherbal compound, suppresses pro-inflammatory mediators and RANKL expression via modulating NFкB and MAPKs signaling pathways in fibroblast-like synoviocytes from adjuvant-induced arthritic rats. Immunol. Res., 2016, 64(4), 1071-1086.
[http://dx.doi.org/10.1007/s12026-016-8794-x] [PMID: 27067226]
[38]
Reich, A.; Szepietowski, J.; Adamski, Z.; Chodorowska, G.; Kaszuba, A.; Krasowska, D.; Lesiak, A.; Maj, J.; Narbutt, J.; Osmola-Mańkowska, A.; Owczarczyk-Saczonek, A.; Owczarek, W.; Placek, W.; Rudnicka, L. Łuszczyca. Rekomendacje diagnostyczno-terapeutyczne Polskiego Towarzystwa Dermatologicznego. Część II: łuszczyca umiarkowana do ciężkiej. Dermatol Rev. Przegl. Dermatol., 2018, 105, 329-357.
[39]
Reich, A.; Adamski, Z.; Chodorowska, G.; Kaszuba, A.; Krasowska, D.; Lesiak, A.; Maj, J.; Narbutt, J.; Osmola-Mańkowska, A.J.; Owczarczyk-Saczonek, A.; Owczarek, W.; Placek, W.J.; Rudnicka, L.; Szepietowski, J. Łuszczyca. Rekomendacje diagnostyczno-terapeutyczne Polskiego Towarzystwa Dermatologicznego. Część 1. Dermatol Rev. Przegl. Dermatol., 2020, 107, 92-108.
[http://dx.doi.org/10.5114/dr.2020.95258]
[40]
Santos, H.; Eusébio, M.; Borges, J.; Gonçalves, D.; Ávila-Ribeiro, P.; Faria, D.S.; Lopes, C.; Rovisco, J.; Águeda, A.; Nero, P.; Valente, P.; Cravo, A.R.; Santos, M.J. Effectiveness of early adalimumab therapy in psoriatic arthritis patients from Reuma.pt - EARLY PsA. Acta Reumatol. Port., 2017, 42(4), 287-299.
[PMID: 29342473]
[41]
Reich, A.; Adamski, Z.; Chodorowska, G.; Kaszuba, A.; Krasowska, D.; Lesiak, A.; Maj, J.; Narbutt, J.; Osmola-Mańkowska, A.; Owczarczyk-Saczonek, A.; Owczarek, W.; Placek, W.; Rudnicka, L.; Szepietowski, J. Łuszczyca. Rekomendacje diagnostyczno-terapeutyczne Polskiego Towarzystwa Dermatologicznego. Część I: łuszczyca łagodna. Dermatol Rev. Przegl. Dermatol., 2018, 105, 224-243.
[42]
Liu, J.T.; Yeh, H.M.; Liu, S.Y.; Chen, K.T. Psoriatic arthritis: Epidemiology, diagnosis, and treatment. World J. Orthop., 2014, 5(4), 537-543.
[http://dx.doi.org/10.5312/wjo.v5.i4.537] [PMID: 25232529]
[43]
Kamata, M.; Tada, Y. Safety of biologics in psoriasis. J. Dermatol., 2018, 45(3), 279-286.
[http://dx.doi.org/10.1111/1346-8138.14096] [PMID: 29226369]
[44]
Nassar, K.; Grisanti, S.; Elfar, E.; Lüke, J.; Lüke, M.; Grisanti, S. Serum cytokines as biomarkers for age-related macular degeneration. Graefes Arch. Clin. Exp. Ophthalmol., 2015, 253(5), 699-704.
[http://dx.doi.org/10.1007/s00417-014-2738-8] [PMID: 25056526]
[45]
Wcisło-Dziadecka, D.; Gola, J.; Grabarek, B.; Mazurek, U.; Brzezińska-Wcisło, L.; Kucharz, E.J. Effect of adalimumab on the expression of genes encoding TNF-α signal paths in skin fibroblasts in vitro. Postepy Dermatol. Alergol., 2018, 35(4), 413-422.
[http://dx.doi.org/10.5114/ada.2018.77673] [PMID: 30206457]
[46]
Enamandram, M.; Kimball, A.B. Psoriasis epidemiology: The interplay of genes and the environment. J. Invest. Dermatol., 2013, 133(2), 287-289.
[http://dx.doi.org/10.1038/jid.2012.434] [PMID: 23318785]
[47]
Nair, R.P.; Duffin, K.C.; Helms, C.; Ding, J.; Stuart, P.E.; Goldgar, D.; Gudjonsson, J.E.; Li, Y.; Tejasvi, T.; Feng, B.J.; Ruether, A.; Schreiber, S.; Weichenthal, M.; Gladman, D.; Rahman, P.; Schrodi, S.J.; Prahalad, S.; Guthery, S.L.; Fischer, J.; Liao, W.; Kwok, P.Y.; Menter, A.; Lathrop, G.M.; Wise, C.A.; Begovich, A.B.; Voorhees, J.J.; Elder, J.T.; Krueger, G.G.; Bowcock, A.M.; Abecasis, G.R. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat. Genet., 2009, 41(2), 199-204.
[http://dx.doi.org/10.1038/ng.311] [PMID: 19169254]
[48]
Capon, F.; Bijlmakers, M.J.; Wolf, N.; Quaranta, M.; Huffmeier, U.; Allen, M.; Timms, K.; Abkevich, V.; Gutin, A.; Smith, R.; Warren, R.B.; Young, H.S.; Worthington, J.; Burden, A.D.; Griffiths, C.E.M.; Hayday, A.; Nestle, F.O.; Reis, A.; Lanchbury, J.; Barker, J.N.; Trembath, R.C. Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene. Hum. Mol. Genet., 2008, 17(13), 1938-1945.
[http://dx.doi.org/10.1093/hmg/ddn091] [PMID: 18364390]

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