Modulation of cell signalling and sulfation in cardiovascular development and disease

Abstract Sulf1/Sulf2 genes are highly expressed during early fetal cardiovascular development but down-regulated during later stages correlating with a number of cell signalling pathways in a positive or a negative manner. Immunocytochemical analysis confirmed SULF1/SULF2 expression not only in endo...

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Autores principales: Tiago Justo, Antonie Martiniuc, Gurtej K. Dhoot
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/8fb1d03a4c0d41338b056f8899ca9223
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spelling oai:doaj.org-article:8fb1d03a4c0d41338b056f8899ca92232021-11-21T12:21:08ZModulation of cell signalling and sulfation in cardiovascular development and disease10.1038/s41598-021-01629-02045-2322https://doaj.org/article/8fb1d03a4c0d41338b056f8899ca92232021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01629-0https://doaj.org/toc/2045-2322Abstract Sulf1/Sulf2 genes are highly expressed during early fetal cardiovascular development but down-regulated during later stages correlating with a number of cell signalling pathways in a positive or a negative manner. Immunocytochemical analysis confirmed SULF1/SULF2 expression not only in endothelial cell lining of blood vessels but also in the developing cardiomyocytes but not in the adult cardiomyocytes despite persisting at reduced levels in the adult endothelial cells. The levels of both SULFs in adult ischemic human hearts and in murine hearts following coronary occlusion increased in endothelial lining of some regional blood vessels but with little or no detection in the cardiomyocytes. Unlike the normal adult heart, the levels of SULF1 and SULF2 were markedly increased in the adult canine right-atrial haemangiosarcoma correlating with increased TGFβ cell signalling. Cell signalling relationship to ischaemia was further confirmed by in vitro hypoxia of HMec1 endothelial cells demonstrating dynamic changes in not only vegf and its receptors but also sulfotransferases and Sulf1 & Sulf2 levels. In vitro hypoxia of HMec1 cells also confirmed earlier up-regulation of TGFβ cell signalling revealed by Smad2, Smad3, ALK5 and TGFβ1 changes and later down-regulation correlating with Sulf1 but not Sulf2 highlighting Sulf1/Sulf2 differences in endothelial cells under hypoxia.Tiago JustoAntonie MartiniucGurtej K. DhootNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Tiago Justo
Antonie Martiniuc
Gurtej K. Dhoot
Modulation of cell signalling and sulfation in cardiovascular development and disease
description Abstract Sulf1/Sulf2 genes are highly expressed during early fetal cardiovascular development but down-regulated during later stages correlating with a number of cell signalling pathways in a positive or a negative manner. Immunocytochemical analysis confirmed SULF1/SULF2 expression not only in endothelial cell lining of blood vessels but also in the developing cardiomyocytes but not in the adult cardiomyocytes despite persisting at reduced levels in the adult endothelial cells. The levels of both SULFs in adult ischemic human hearts and in murine hearts following coronary occlusion increased in endothelial lining of some regional blood vessels but with little or no detection in the cardiomyocytes. Unlike the normal adult heart, the levels of SULF1 and SULF2 were markedly increased in the adult canine right-atrial haemangiosarcoma correlating with increased TGFβ cell signalling. Cell signalling relationship to ischaemia was further confirmed by in vitro hypoxia of HMec1 endothelial cells demonstrating dynamic changes in not only vegf and its receptors but also sulfotransferases and Sulf1 & Sulf2 levels. In vitro hypoxia of HMec1 cells also confirmed earlier up-regulation of TGFβ cell signalling revealed by Smad2, Smad3, ALK5 and TGFβ1 changes and later down-regulation correlating with Sulf1 but not Sulf2 highlighting Sulf1/Sulf2 differences in endothelial cells under hypoxia.
format article
author Tiago Justo
Antonie Martiniuc
Gurtej K. Dhoot
author_facet Tiago Justo
Antonie Martiniuc
Gurtej K. Dhoot
author_sort Tiago Justo
title Modulation of cell signalling and sulfation in cardiovascular development and disease
title_short Modulation of cell signalling and sulfation in cardiovascular development and disease
title_full Modulation of cell signalling and sulfation in cardiovascular development and disease
title_fullStr Modulation of cell signalling and sulfation in cardiovascular development and disease
title_full_unstemmed Modulation of cell signalling and sulfation in cardiovascular development and disease
title_sort modulation of cell signalling and sulfation in cardiovascular development and disease
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/8fb1d03a4c0d41338b056f8899ca9223
work_keys_str_mv AT tiagojusto modulationofcellsignallingandsulfationincardiovasculardevelopmentanddisease
AT antoniemartiniuc modulationofcellsignallingandsulfationincardiovasculardevelopmentanddisease
AT gurtejkdhoot modulationofcellsignallingandsulfationincardiovasculardevelopmentanddisease
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