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ZMPSTE24 Is Associated with Elevated Inflammation and Progerin mRNA

Lamins are important filaments forming the inner nuclear membrane. Lamin A is processed by zinc metalloproteinase (ZMPSTE24). Failure to cleave a truncated form of prelamin A—also called progerin—causes Hutchinson–Gilford progeria syndrome a well-known premature aging disease. Minor levels of proger...

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Autores principales: Messner, Moritz, Ghadge, Santhosh Kumar, Maurer, Thomas, Graber, Michael, Staggl, Simon, Christine Maier, Sarah, Pölzl, Gerhard, Zaruba, Marc-Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563344/
https://www.ncbi.nlm.nih.gov/pubmed/32872320
http://dx.doi.org/10.3390/cells9091981
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author Messner, Moritz
Ghadge, Santhosh Kumar
Maurer, Thomas
Graber, Michael
Staggl, Simon
Christine Maier, Sarah
Pölzl, Gerhard
Zaruba, Marc-Michael
author_facet Messner, Moritz
Ghadge, Santhosh Kumar
Maurer, Thomas
Graber, Michael
Staggl, Simon
Christine Maier, Sarah
Pölzl, Gerhard
Zaruba, Marc-Michael
author_sort Messner, Moritz
collection PubMed
description Lamins are important filaments forming the inner nuclear membrane. Lamin A is processed by zinc metalloproteinase (ZMPSTE24). Failure to cleave a truncated form of prelamin A—also called progerin—causes Hutchinson–Gilford progeria syndrome a well-known premature aging disease. Minor levels of progerin are readily expressed in the blood of healthy individuals due to alternative splicing. Previously, we found an association of increased progerin mRNA with overweight and chronic inflammation (hs-CRP). Here, we aimed to elucidate correlations of ZMPSTE24, lamin A/C and progerin with the inflammatory marker hs-CRP. In this retrospective, cross-sectional study we analyzed blood samples from 110 heart failure patients for quantitative mRNA expression of ZMPSTE24, lamin A/C, progerin and hs-CRP protein. Spearman correlations and linear regression analyses including adjustments for age, gender and ejection fraction showed a significant positive correlation of lnprogerin with lnZMPSTE24 (n = 110; r = 0.33; p = 0.0004) and lnlamin A/C (n = 110; r = 0.82, p < 0.0001), whereas no association was observed between lnlamin A/C and lnZMPSTE24 expression. Further analyses showed a significant positive correlation of lnhs-CRP with lnZMPSTE24 (n = 110; r = 0.21; p = 0.01) and lnlamin A/C (n = 110; r = 0.24; p = 0.03). We conclude that chronic inflammation is associated with increased expression of ZMPSTE24 and lamin A/C mRNA. Both markers also positively correlate with increased expression of the premature aging marker progerin which may be linked to cardiovascular aging.
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spelling pubmed-75633442020-10-27 ZMPSTE24 Is Associated with Elevated Inflammation and Progerin mRNA Messner, Moritz Ghadge, Santhosh Kumar Maurer, Thomas Graber, Michael Staggl, Simon Christine Maier, Sarah Pölzl, Gerhard Zaruba, Marc-Michael Cells Article Lamins are important filaments forming the inner nuclear membrane. Lamin A is processed by zinc metalloproteinase (ZMPSTE24). Failure to cleave a truncated form of prelamin A—also called progerin—causes Hutchinson–Gilford progeria syndrome a well-known premature aging disease. Minor levels of progerin are readily expressed in the blood of healthy individuals due to alternative splicing. Previously, we found an association of increased progerin mRNA with overweight and chronic inflammation (hs-CRP). Here, we aimed to elucidate correlations of ZMPSTE24, lamin A/C and progerin with the inflammatory marker hs-CRP. In this retrospective, cross-sectional study we analyzed blood samples from 110 heart failure patients for quantitative mRNA expression of ZMPSTE24, lamin A/C, progerin and hs-CRP protein. Spearman correlations and linear regression analyses including adjustments for age, gender and ejection fraction showed a significant positive correlation of lnprogerin with lnZMPSTE24 (n = 110; r = 0.33; p = 0.0004) and lnlamin A/C (n = 110; r = 0.82, p < 0.0001), whereas no association was observed between lnlamin A/C and lnZMPSTE24 expression. Further analyses showed a significant positive correlation of lnhs-CRP with lnZMPSTE24 (n = 110; r = 0.21; p = 0.01) and lnlamin A/C (n = 110; r = 0.24; p = 0.03). We conclude that chronic inflammation is associated with increased expression of ZMPSTE24 and lamin A/C mRNA. Both markers also positively correlate with increased expression of the premature aging marker progerin which may be linked to cardiovascular aging. MDPI 2020-08-28 /pmc/articles/PMC7563344/ /pubmed/32872320 http://dx.doi.org/10.3390/cells9091981 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Messner, Moritz
Ghadge, Santhosh Kumar
Maurer, Thomas
Graber, Michael
Staggl, Simon
Christine Maier, Sarah
Pölzl, Gerhard
Zaruba, Marc-Michael
ZMPSTE24 Is Associated with Elevated Inflammation and Progerin mRNA
title ZMPSTE24 Is Associated with Elevated Inflammation and Progerin mRNA
title_full ZMPSTE24 Is Associated with Elevated Inflammation and Progerin mRNA
title_fullStr ZMPSTE24 Is Associated with Elevated Inflammation and Progerin mRNA
title_full_unstemmed ZMPSTE24 Is Associated with Elevated Inflammation and Progerin mRNA
title_short ZMPSTE24 Is Associated with Elevated Inflammation and Progerin mRNA
title_sort zmpste24 is associated with elevated inflammation and progerin mrna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563344/
https://www.ncbi.nlm.nih.gov/pubmed/32872320
http://dx.doi.org/10.3390/cells9091981
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