Abstract
Migraine is a complex disabling condition which is associated with dysregulation of several pathways particularly those being associated with immune responses. In order to assess contribution of protein inhibitor of activated STAT (PIAS) in the pathogenesis of migraine, we quantified expression levels of PIAS1–PIAS4 genes in the circulation of patients with migraine compared with controls. Expression of PIAS1 was substantially lower in total migraineurs compared with controls (ratio of mean expressions (RME) = 0.18, SE = 0.29, P value < 0.001) and in both male and female migraineurs compared with sex-matched controls. Expression of PIAS2 was lower in migraineurs without aura compared with controls (RME = 0.64, SE = 0.31, P value = 0.04) and in male subgroup of these patients compared with male controls (RME = 0.60, SE = 0.22, P value < 0.001). In migraineurs with aura, downregulation of PIAS2 was only observed among male subgroups (RME = 0.37, SE = 0.49, P value = 0.01). PIAS3 was downregulated in total male migraineurs (RME = 0.52, SE = 0.43, P value = 0.04) and in male migraineurs with aura (RME = 0.49, SE = 0.45, P value = 0.03) compared with male controls. Finally, PIAS4 was upregulated in total migraineurs (RME = 3.78, SE = 0. 34, P value < 0.001), female migraineurs (RME = 5.26, SE = 0.36, P value < 0.001), migraineurs with aura (RME = 4.24, SE = 0.42, P value < 0.001), female migraineurs with aura (RME = 6.13, SE = 0.47, P value < 0.001), migraineurs without aura (RME = 3.33, SE = 0.38, P value < 0.001), and female migraineurs without aura (RME = 4.47, SE = 0.41, P value < 0.001) compared with the corresponding controls. The present study suggests contribution of PIAS genes in the pathogenesis of migraine and warrants future studies to clarify the functional routes of their contribution.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
The analyzed data sets generated during the study are available from the corresponding author on reasonable request.
References
Andreou AP, Edvinsson L (2019) Mechanisms of migraine as a chronic evolutive condition. The Journal Of Headache And Pain 20:1–17
Bao C, Li Y, Huan L, Zhang Y, Zhao F, Wang Q, Liang L, Ding J, Liu L, Chen T (2015) Nf-Κb signaling relieves negative regulation by Mir-194 in hepatocellular carcinoma by suppressing the transcription factor Hnf-1α. Sci Signal 8:Ra75-Ra75.
Bruno P, Carpino F, Carpino G, Zicari A (2007a) An overview on immune system and migraine. European Review For Medical And Pharmacological Sciences 11:245
Bruno PP, Carpino F, Carpino G, Zicari A (2007b) An overview on immune system and migraine. Eur Rev Med Pharmacol Sci 11:245–248
Ebahimzadeh K, Gholipour M, Samadian M, Taheri M Ghafouri-Fard S (2021) A comprehensive review on the role of genetic factors in the pathogenesis of migraine. J Mol Neurosci
Galeotti N, Ghelardini C (2013) Inhibition of the Pkcγ-Ε pathway relieves from meningeal nociception in an animal model: an innovative perspective for migraine therapy? Neurotherapeutics 10:329–339
Jacobs B, Dussor G (2016) Neurovascular contributions to migraine: moving beyond vasodilation. Neuroscience 338:130–144
Kato T Jr, Gotoh Y, Hoffmann A, Ono Y (2008) Negative regulation of constitutive Nf-Κb and Jnk signaling by Pkn1-mediated phosphorylation of Traf1. Genes Cells 13:509–520
Kubota T, Matsuoka M, Xu S, Otsuki N, Takeda M, Kato A, Ozato K (2011) Piasy inhibits virus-induced and interferon-stimulated transcription through distinct mechanisms. J Biol Chem 286:8165–8175
Liu B, Liao J, Rao X, Kushner SA, Chung CD, Chang DD, Shuai K (1998) Inhibition of Stat1-mediated gene activation by Pias1. Proc Natl Acad Sci USA 95:10626–10631
Niu GJ, Xu JD, Yuan WJ, Sun JJ, Yang MC, He ZH, Zhao XF, Wang JX (2018) Protein inhibitor of activated Stat (Pias) negatively regulates the Jak/Stat pathway by inhibiting Stat phosphorylation and translocation. Front Immunol 9:2392
Olesen J (2018) International classification of headache disorders. The Lancet Neurology 17:396–397
Sayad A, Taheri M, Azari I, Oskoei VK, Ghafouri-Fard S (2019) Pias genes as disease markers in bipolar disorder. J Cell Biochem 120:12937–12942
Shuai K, Liu B (2005) Regulation of gene-activation pathways by pias proteins in the immune system. Nat Rev Immunol 5:593–605
Sprague AH, Khalil RA (2009) Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol 78:539–552
Taheri M, Azimi G, Sayad A, Mazdeh M, Arsang-Jang S, Omrani MD, Ghafouri-Fard S (2018) Expression analysis of protein inhibitor of activated Stat (Pias) genes in Ifnβ-treated multiple sclerosis patients. J Inflamm Res 11:457–463
Taheri M, Nicknafs F, Hesami O, Javadi A, Arsang-Jang S, Sayad A Ghafouri-Fard S (2020) Differential expression of cytokine-coding genes among migraine patients with and without aura and normal subjects. J Mol Neurosci
Taheri M, Oskooei VK, Ghafouri-Fard S (2019) Protein inhibitor of activated Stat genes are differentially expressed in breast tumor tissues. Pers Med 16:277–285
Tolkunova E, Malashicheva A, Parfenov VN, Sustmann C, Grosschedl R, Tomilin A (2007) Pias proteins as repressors of Oct4 function. J Mol Biol 374:1200–1212
Yi L, Wu Q, Chen N, Song G, Wang C, Zou Q, Zhang Z (2018) Valproate plays a protective role against migraine by inhibiting protein kinase C signalling in nitroglycerin-treated mice. Basic Clin Pharmacol Toxicol 122:310–316
Funding
The current study was supported by a grant from Shahid Beheshti University of Medical Sciences.
Author information
Authors and Affiliations
Contributions
As and SGF wrote the draft and revised it. MT and OH performed the experiment. NN analyzed the data. All authors contributed equally and fully aware of submission.
Corresponding authors
Ethics declarations
Informed Consent
Informed consent forms were obtained from all study participants. The study protocol was approved by the ethical committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.RETECH.REC.1399.856). All methods were performed in accordance with the relevant guidelines and regulations.
Research Involving Human and Animals
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards
Competing Interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Ghafouri-Fard, S., Hesami, O., Nazer, N. et al. Expression of PIAS Genes in Migraine Patients. J Mol Neurosci 71, 2053–2059 (2021). https://doi.org/10.1007/s12031-021-01834-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-021-01834-6