MicroRNA-941 Expression in Polymorphonuclear Granulocytes Is Not Related to Granulomatosis with Polyangiitis
| Autor: | Nicolas Rapin, Niels Borregaard, Jesper Brink Svendsen, Jack B. Cowland, Elisabeth Præstekjær Cramer, Bo Baslund |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Jumonji Domain-Containing Histone Demethylases Neutrophils lcsh:Medicine Gene Expression Biochemistry Monocytes Lysine demethylase 6B White Blood Cells Animal Cells Proteinase 3 Gene expression Medicine and Health Sciences lcsh:Science Aged 80 and over Principal Component Analysis Multidisciplinary Messenger RNA Transfection Middle Aged Nucleic acids Female Cellular Types Granulomatosis with polyangiitis Research Article Adult Immune Cells Myeloblastin Immunology CD16 Biology GPI-Linked Proteins Autoimmune Diseases Young Adult 03 medical and health sciences microRNA Genetics medicine Humans RNA Messenger Wegener Granulomatosis Non-coding RNA Blood Cells 030102 biochemistry & molecular biology lcsh:R Receptors IgG Granulomatosis with Polyangiitis Biology and Life Sciences Cell Biology medicine.disease Molecular biology Gene regulation MicroRNAs 030104 developmental biology Case-Control Studies RNA lcsh:Q Clinical Immunology Clinical Medicine Transcriptome Granulocytes Promyelocyte |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 10, p e0164985 (2016) |
| ISSN: | 1932-6203 |
| Popis: | Jumonji Domain-Containing Protein 3 (JMJD3)/lysine demethylase 6B (KDM6B) is an epigenetic modulator that removes repressive histone marks on genes. Expression of KDM6B mRNA is elevated in leukocytes from patients with ANCA-associated vasculitis (AAV) and has been suggested to be the reason for higher proteinase 3 (PR3) mRNA expression in these cells due to derepression of PRTN3 gene transcription. MicroRNA-941 (miR-941) has been shown to target KDM6B mRNA and inhibit JMJD3 production. We therefore investigated whether polymorphonuclear granulocytes (PMNs) from patients suffering from granulomatosis with polyangiitis (GPA) have lower expression of miR-941 than healthy control donors as a biological cause for higher JMJD3 levels. We found no significant difference in the degree of maturation of PMNs from GPA patients (n = 8) and healthy controls (n = 11) as determined from cell surface expression of the neutrophil maturation marker CD16 and gene expression profile of FCGR3B. The expression of PRTN3 and KDM6B mRNAs and miR-941 was not significantly different in GPA patients and healthy controls. Transfection of pre-miR-941 into the neutrophil promyelocyte cell line PLB-985 cells did not result in reduction of the KDM6B mRNA level as shown previously in a hepatocellular carcinoma cell line. The amount of PR3 in PMNs from GPA patients and healthy controls was comparable. In conclusion, we found that PRTN3 mRNA, KDM6B mRNA, and miR-941 expression levels in PMNs do not differ between GPA patients and healthy controls, and that miR-941 does not uniformly regulate KDM6B mRNA levels by inducing degradation of the transcript. Thus, decreased miR-941 expression in PMNs cannot be part of the pathogenesis of GPA. |
| Databáze: | OpenAIRE |
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