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MicroRNA-941 Expression in Polymorphonuclear Granulocytes Is Not Related to Granulomatosis with Polyangiitis

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 high...

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Autores principales: Svendsen, Jesper Brink, Baslund, Bo, Cramer, Elisabeth Præstekjær, Rapin, Nicolas, Borregaard, Niels, Cowland, Jack Bernard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068789/
https://www.ncbi.nlm.nih.gov/pubmed/27755585
http://dx.doi.org/10.1371/journal.pone.0164985
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author Svendsen, Jesper Brink
Baslund, Bo
Cramer, Elisabeth Præstekjær
Rapin, Nicolas
Borregaard, Niels
Cowland, Jack Bernard
author_facet Svendsen, Jesper Brink
Baslund, Bo
Cramer, Elisabeth Præstekjær
Rapin, Nicolas
Borregaard, Niels
Cowland, Jack Bernard
author_sort Svendsen, Jesper Brink
collection PubMed
description 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.
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spelling pubmed-50687892016-10-27 MicroRNA-941 Expression in Polymorphonuclear Granulocytes Is Not Related to Granulomatosis with Polyangiitis Svendsen, Jesper Brink Baslund, Bo Cramer, Elisabeth Præstekjær Rapin, Nicolas Borregaard, Niels Cowland, Jack Bernard PLoS One Research Article 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. Public Library of Science 2016-10-18 /pmc/articles/PMC5068789/ /pubmed/27755585 http://dx.doi.org/10.1371/journal.pone.0164985 Text en © 2016 Svendsen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Svendsen, Jesper Brink
Baslund, Bo
Cramer, Elisabeth Præstekjær
Rapin, Nicolas
Borregaard, Niels
Cowland, Jack Bernard
MicroRNA-941 Expression in Polymorphonuclear Granulocytes Is Not Related to Granulomatosis with Polyangiitis
title MicroRNA-941 Expression in Polymorphonuclear Granulocytes Is Not Related to Granulomatosis with Polyangiitis
title_full MicroRNA-941 Expression in Polymorphonuclear Granulocytes Is Not Related to Granulomatosis with Polyangiitis
title_fullStr MicroRNA-941 Expression in Polymorphonuclear Granulocytes Is Not Related to Granulomatosis with Polyangiitis
title_full_unstemmed MicroRNA-941 Expression in Polymorphonuclear Granulocytes Is Not Related to Granulomatosis with Polyangiitis
title_short MicroRNA-941 Expression in Polymorphonuclear Granulocytes Is Not Related to Granulomatosis with Polyangiitis
title_sort microrna-941 expression in polymorphonuclear granulocytes is not related to granulomatosis with polyangiitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068789/
https://www.ncbi.nlm.nih.gov/pubmed/27755585
http://dx.doi.org/10.1371/journal.pone.0164985
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