Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence

Abstract Senescence in placenta/fetal membranes is a normal phenomenon linked to term parturition. However, excessive senescence which may be induced by telomere attrition, has been associated with preeclampsia (PE). We hypothesized that the telomerase complex in peripheral blood mononuclear cells (...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	T. Lekva, M. C. P. Roland, M. E. Estensen, E. R. Norwitz, T. Tilburgs, T. Henriksen, J. Bollerslev, K. R. Normann, P. Magnus, O. K. Olstad, P. Aukrust, T. Ueland
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/71ebd5ffe5f54d9cbc9e34dbe0b359d1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:71ebd5ffe5f54d9cbc9e34dbe0b359d1
record_format	dspace
spelling	oai:doaj.org-article:71ebd5ffe5f54d9cbc9e34dbe0b359d12021-12-02T18:09:03ZDysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence10.1038/s41598-021-99140-z2045-2322https://doaj.org/article/71ebd5ffe5f54d9cbc9e34dbe0b359d12021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99140-zhttps://doaj.org/toc/2045-2322Abstract Senescence in placenta/fetal membranes is a normal phenomenon linked to term parturition. However, excessive senescence which may be induced by telomere attrition, has been associated with preeclampsia (PE). We hypothesized that the telomerase complex in peripheral blood mononuclear cells (PBMC) and circulating telomere associated senescence markers would be dysregulated in women with PE. We measured long non-coding (nc) RNA telomerase RNA component (TERC) and RNAs involved in the maturation of TERC in PBMC, and the expression of TERC and 5′–3′ Exoribonuclease 1 (XRN1) in extracellular vesicles at 22–24 weeks, 36–38 weeks and, 5-year follow-up in controls and PE. We also measured telomere length at 22–24 weeks and 5-year follow-up. The circulating senescence markers cathelicidin antimicrobial peptide (CAMP), β-galactosidase, stathmin 1 (STMN1) and chitotriosidase/CHIT1 were measured at 14–16, 22–24, 36–38 weeks and at 5-year follow-up in the STORK study and before delivery and 6 months post-partum in the ACUTE PE study. We found decreased expression of TERC in PBMC early in pregnant women who subsequently developed PE. XRN1 involved in the maturation of TERC was also reduced in pregnancy and 5-year follow-up. Further, we found that the senescence markers CAMP and β-galactosidase were increased in PE pregnancies, and CAMP remained higher at 5-year follow-up. β-galactosidase was associated with atherogenic lipid ratios during pregnancy and at 5-year follow-up, in PE particularly. This study suggests a potential involvement of dysfunctional telomerase biology in the pathophysiology of PE, which is not restricted to the placenta.T. LekvaM. C. P. RolandM. E. EstensenE. R. NorwitzT. TilburgsT. HenriksenJ. BollerslevK. R. NormannP. MagnusO. K. OlstadP. AukrustT. UelandNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q T. Lekva M. C. P. Roland M. E. Estensen E. R. Norwitz T. Tilburgs T. Henriksen J. Bollerslev K. R. Normann P. Magnus O. K. Olstad P. Aukrust T. Ueland Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence
description	Abstract Senescence in placenta/fetal membranes is a normal phenomenon linked to term parturition. However, excessive senescence which may be induced by telomere attrition, has been associated with preeclampsia (PE). We hypothesized that the telomerase complex in peripheral blood mononuclear cells (PBMC) and circulating telomere associated senescence markers would be dysregulated in women with PE. We measured long non-coding (nc) RNA telomerase RNA component (TERC) and RNAs involved in the maturation of TERC in PBMC, and the expression of TERC and 5′–3′ Exoribonuclease 1 (XRN1) in extracellular vesicles at 22–24 weeks, 36–38 weeks and, 5-year follow-up in controls and PE. We also measured telomere length at 22–24 weeks and 5-year follow-up. The circulating senescence markers cathelicidin antimicrobial peptide (CAMP), β-galactosidase, stathmin 1 (STMN1) and chitotriosidase/CHIT1 were measured at 14–16, 22–24, 36–38 weeks and at 5-year follow-up in the STORK study and before delivery and 6 months post-partum in the ACUTE PE study. We found decreased expression of TERC in PBMC early in pregnant women who subsequently developed PE. XRN1 involved in the maturation of TERC was also reduced in pregnancy and 5-year follow-up. Further, we found that the senescence markers CAMP and β-galactosidase were increased in PE pregnancies, and CAMP remained higher at 5-year follow-up. β-galactosidase was associated with atherogenic lipid ratios during pregnancy and at 5-year follow-up, in PE particularly. This study suggests a potential involvement of dysfunctional telomerase biology in the pathophysiology of PE, which is not restricted to the placenta.
format	article
author	T. Lekva M. C. P. Roland M. E. Estensen E. R. Norwitz T. Tilburgs T. Henriksen J. Bollerslev K. R. Normann P. Magnus O. K. Olstad P. Aukrust T. Ueland
author_facet	T. Lekva M. C. P. Roland M. E. Estensen E. R. Norwitz T. Tilburgs T. Henriksen J. Bollerslev K. R. Normann P. Magnus O. K. Olstad P. Aukrust T. Ueland
author_sort	T. Lekva
title	Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence
title_short	Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence
title_full	Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence
title_fullStr	Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence
title_full_unstemmed	Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence
title_sort	dysregulated non-coding telomerase rna component and associated exonuclease xrn1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/71ebd5ffe5f54d9cbc9e34dbe0b359d1
work_keys_str_mv	AT tlekva dysregulatednoncodingtelomerasernacomponentandassociatedexonucleasexrn1inleucocytesfromwomendevelopingpreeclampsiapossiblelinktoenhancedsenescence AT mcproland dysregulatednoncodingtelomerasernacomponentandassociatedexonucleasexrn1inleucocytesfromwomendevelopingpreeclampsiapossiblelinktoenhancedsenescence AT meestensen dysregulatednoncodingtelomerasernacomponentandassociatedexonucleasexrn1inleucocytesfromwomendevelopingpreeclampsiapossiblelinktoenhancedsenescence AT ernorwitz dysregulatednoncodingtelomerasernacomponentandassociatedexonucleasexrn1inleucocytesfromwomendevelopingpreeclampsiapossiblelinktoenhancedsenescence AT ttilburgs dysregulatednoncodingtelomerasernacomponentandassociatedexonucleasexrn1inleucocytesfromwomendevelopingpreeclampsiapossiblelinktoenhancedsenescence AT thenriksen dysregulatednoncodingtelomerasernacomponentandassociatedexonucleasexrn1inleucocytesfromwomendevelopingpreeclampsiapossiblelinktoenhancedsenescence AT jbollerslev dysregulatednoncodingtelomerasernacomponentandassociatedexonucleasexrn1inleucocytesfromwomendevelopingpreeclampsiapossiblelinktoenhancedsenescence AT krnormann dysregulatednoncodingtelomerasernacomponentandassociatedexonucleasexrn1inleucocytesfromwomendevelopingpreeclampsiapossiblelinktoenhancedsenescence AT pmagnus dysregulatednoncodingtelomerasernacomponentandassociatedexonucleasexrn1inleucocytesfromwomendevelopingpreeclampsiapossiblelinktoenhancedsenescence AT okolstad dysregulatednoncodingtelomerasernacomponentandassociatedexonucleasexrn1inleucocytesfromwomendevelopingpreeclampsiapossiblelinktoenhancedsenescence AT paukrust dysregulatednoncodingtelomerasernacomponentandassociatedexonucleasexrn1inleucocytesfromwomendevelopingpreeclampsiapossiblelinktoenhancedsenescence AT tueland dysregulatednoncodingtelomerasernacomponentandassociatedexonucleasexrn1inleucocytesfromwomendevelopingpreeclampsiapossiblelinktoenhancedsenescence
_version_	1718378635951341568

Dysregulated non-coding telomerase RNA component and associated exonuclease XRN1 in leucocytes from women developing preeclampsia-possible link to enhanced senescence

Ejemplares similares