Mineralocorticoid Receptor Signaling in Peripheral Blood Cells in Patients with Multiple Sclerosis

Multiple sclerosis (MS) is associated with alterations in neuroendocrine function, primarily the hypothalamic-pituitary-adrenal axis, including lower expression of the glucocorticoid receptor (GR) and its target genes in peripheral blood mononuclear cells (PBMC) or full blood. We previously found re...

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Bibliographic Details
Published in:	International journal of molecular sciences Vol. 25; no. 16; p. 8883
Main Authors:	Küstermann, Franziska, Busse, Kathy, Orthgieß, Johannes, Stoppe, Muriel, Haars, Sarah, Then Bergh, Florian
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 15-08-2024 MDPI
Subjects:	Adult aldosterone Disease Female Genes Humans Immune system Influence Interferon Leukocytes, Mononuclear - metabolism Lymphocytes Male Middle Aged mineralocorticoid receptor Multiple sclerosis Multiple Sclerosis - blood Multiple Sclerosis - drug therapy Multiple Sclerosis - genetics Multiple Sclerosis - metabolism Multiple Sclerosis - pathology Pathogenesis Patients Receptors, Mineralocorticoid - genetics Receptors, Mineralocorticoid - metabolism Signal Transduction target gene transcriptional regulation mineralocorticoid receptor aldosterone multiple sclerosis target gene transcriptional regulation
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Summary:	Multiple sclerosis (MS) is associated with alterations in neuroendocrine function, primarily the hypothalamic-pituitary-adrenal axis, including lower expression of the glucocorticoid receptor (GR) and its target genes in peripheral blood mononuclear cells (PBMC) or full blood. We previously found reduced mineralocorticoid receptor (MR) expression in MS patients' peripheral blood. MS is being treated with a widening variety of disease-modifying treatments (DMT), some of which have similar efficacy but different mechanisms of action; body-fluid biomarkers to support the choice of the optimal initial DMT and/or to indicate an unsatisfactory response before clinical activity are unavailable. Using cell culture of volunteers' PBMCs and subsequent gene expression analysis (microarray and qPCR validation), we identified the mRNA expression of OTUD1 to represent MR signaling. The MR and MR target gene expression levels were then measured in full blood samples. In 119 MS (or CIS) patients, the expression of both MR and OTUD1 was lower than in 42 controls. The expression pattern was related to treatment, with the MR expression being particularly low in patients treated with fingolimod. While MR signaling may be involved in the therapeutic effects of some disease-modifying treatments, MR and OTUD1 expression can complement the neuroendocrine assessment of MS disease course. If confirmed, such assessment may support clinical decision-making.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current Address: Sächsisches Krankenhaus Altscherbitz, Klinik für Neurologie, 04435 Schkeuditz, Germany.
ISSN:	1661-6596 1422-0067 1422-0067
DOI:	10.3390/ijms25168883