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

Krawczyk, Agata; Strzałka‐Mrozik, Barbara; Juszczyk, Karol; Kimsa-Dudek, Magdalena; Wcisło‐Dziadecka, Dominika; Gola, Joanna

doi:10.2174/1389201023666220628111644

Cited by 3 publications

(1 citation statement)

References 42 publications

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“…Only in the case of MAP2K2 , its expression is not regulated by miRNA molecules. Nevertheless, Krawczyk et al suggest that MAP2K2 mRNA may be considered as a molecular marker of response to adalimumab treatment for psoriatic arthritis [ 101 ].…”

Section: Discussionmentioning

confidence: 99%

Expression profile of mRNAs and miRNAs related to mitogen-activated kinases in HaCaT cell culture treated with lipopolysaccharide a and adalimumab

Wójcik,

Plata-Babula,

Głowaczewska

et al. 2024

Cell Cycle

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Studies indicate that mitogen-activated protein kinases (MAPKs) exhibit activation and overexpression within psoriatic lesions. This study aimed to investigate alterations in the expression patterns of genes encoding MAPKs and microRNA (miRNA) molecules that potentially regulate their expression in human adult low-calcium high-temperature (HaCaT) keratinocytes when exposed to bacterial lipopolysaccharide A (LPS) and adalimumab. HaCaT cells underwent treatment with 1 µg/mL LPS for 8 hours, followed by treatment with 8 µg/mL adalimumab for 2, 8, or 24 hours. Untreated cells served as controls. The molecular analysis involved microarray, quantitative real-time polymerase chain reaction (RTqPCR), and enzyme-linked immunosorbent assay (ELISA) analyses. Changes in the expression profile of seven mRNAs: dual specificity phosphatase 1 ( DUSP1) , dual specificity phosphatase 3 ( DUSP3) , dual specificity phosphatase 4 ( DUSP4) , mitogen-activated protein kinase 9 ( MAPK9) , mitogen-activated protein kinase kinase kinase 2 ( MAP3K2) , mitogen-activated protein kinase kinase 2 ( MAP2K2), and MAP kinase-activated protein kinase 2 (MAPKAPK2 , also known as MK2) in cell culture exposed to LPS or LPS and the drug compared to the control. It was noted that miR-34a may potentially regulate the activity of DUSP1 , DUSP3 , and DUSP4 , while miR-1275 is implicated in regulating MAPK9 expression. Additionally, miR-382 and miR-3188 are potential regulators of DUSP4 levels, and miR-200-5p is involved in regulating MAPKAPK2 and MAP3K2 levels. Thus, the analysis showed that these mRNA molecules and the proteins and miRNAs they encode appear to be useful molecular markers for monitoring the efficacy of adalimumab therapy.

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Section: Discussionmentioning

confidence: 99%

Expression profile of mRNAs and miRNAs related to mitogen-activated kinases in HaCaT cell culture treated with lipopolysaccharide a and adalimumab

Wójcik,

Plata-Babula,

Głowaczewska

et al. 2024

Cell Cycle

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Modulation of IL-6 receptor/STAT3 downstream signaling in rheumatoid arthritis patients

Cacciapaglia,

Perniola,

Stano

et al. 2025

Experimental and Molecular Pathology

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Variances in the Expression Profile of DUSP1-7 and miRNAs Regulating their Expression in the HaCat Line under LPS and Cyclosporine A

Dąbala¹,

Świder²,

Kasela³

et al. 2023

CPB

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Introduction: Cyclosporin A (CsA) treats moderate to severe psoriasis vulgaris. Psoriasis is a chronic inflammatory disease in which hyperproliferation of keratinocytes occurs. One of the most relevant signaling cascades in the development of psoriasis is the mitogen-activated protein kinase (MAPK) signaling pathway. It has been observed that dual-specificity phosphatases (DUSPs) dephosphorylate signaling molecules, such as MAPKs. background: Cyclosporin A (CsA) is used to treat moderate to severe psoriasis vulgaris. Psoriasis is a chronic inflammatory disease in which hyperproliferation of keratinocytes is noted. One of the most relevant signaling cascades in the development of psoriasis is the mitogen-activated protein kinase (MAPK) signaling pathway Dual-specificity phosphatases (DUSPs) dephosphorylate signaling molecules such as MAPKs. Aims: Aims: This study aims to determine changes in the expression pattern of Dual Activity Protein Phosphatase (DUSP1-7) and micro RNAs (miRNAs), potentially regulating their expression in the human adult, low-calcium, high-temperature keratinocytes cell line (HaCaT) cultures exposed to lipopolysaccharide A (LPS)-induced inflammation, followed by CsA. Methods: HaCaT cell line was exposed for 8 hours to 1 μg/mL LPS and then to 100 ng/mL CsA for 2, 8, and 24 hours compared to cultures not exposed to LPS and the drug. The molecular analysis included determining the DUSP1-7 expression and the miRNAs potentially regulating it using an expression microarray technique. An enzyme-linked immunosorbent assay (ELISA) was also performed to assess the concentration of DUSP1-7 in the culture medium. Statistical evaluation was performed assuming a statistical significance threshold (p) of < 0.05. method: Human keratinocyte (HaCaT) cell line was exposed for 8 hours to 1 μg/mL LPS and then to 100 ng/mL CsA for 2, 8, and 24 hours compared to cultures not exposed to LPS and the drug. The molecular analysis included determining DUSP1-7 expression and the miRNAs potentially regulating its expression by expression microarray technique. An Enzyme-Linked immunosorbent assay (ELISA) was also performed to assess the concentration of DUSP1-7 in the culture medium. Statistical evaluation was performed assuming a statistical significance threshold (p) < 0.05. Results: Statistically significant differences were found in the expression of DUSP1-7 mRNAs and the miRNAs that regulate their expression. The most significant changes in expression were observed for DUSP1 and DUSP5, with the differences being most pronounced during the eight-hour incubation period of the cells, with the drug predictive analysis showing that miR-34 potentially regulates the expression of DUSP1-4,7, miR-1275: DUSP2, mir-3188:DUSP4, miR-382: DUSP4, miR-27a and miR-27b: DUSP5,6 and miR-16: DUSP7. No expression of DUSP1-7 was demonstrated at the protein level in CsA-exposed cultures. Conclusion: Our evaluation of the efficacy of CsA therapy on an in vitro model of HaCaT indicates that treatment with this drug is effective, resulting in changes in the expression of DUSP1-7 and, potentially, the miRNAs that regulate their expression. We also confirmed that the different expression pattern of mRNA and protein encoded by a given transcript is not only due to the regulatory role of miRNAs but also the lack of synchronization between transcription and translation processes. conclusion: Our evaluation of the efficacy of CsA therapy on an in vitro model of HaCaT indicates that treatment with this drug is effective, resulting in the observed changes in the expression of DUSP1-7 and, potentially, the miRNAs that regulate their expression. We also confirmed that the different expression pattern of mRNA and protein encoded by a given transcript is not only due to the regulatory role of miRNAs but also to the lack of synchronization between transcription and translation processes.

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

Cited by 3 publications

References 42 publications

Expression profile of mRNAs and miRNAs related to mitogen-activated kinases in HaCaT cell culture treated with lipopolysaccharide a and adalimumab

Expression profile of mRNAs and miRNAs related to mitogen-activated kinases in HaCaT cell culture treated with lipopolysaccharide a and adalimumab

Modulation of IL-6 receptor/STAT3 downstream signaling in rheumatoid arthritis patients

Variances in the Expression Profile of DUSP1-7 and miRNAs Regulating their Expression in the HaCat Line under LPS and Cyclosporine A

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