Cytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome

Fibroblasts contribute to approximately 20% of the non-cardiomyocytic cells in the heart. They play important roles in the myocardial adaption to stretch, inflammation, and other pathophysiological conditions. Fibroblasts are a major source of extracellular matrix (ECM) proteins whose production is...

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Autores principales:	Hanna Bräuninger, Tilo Thottakara, Jacob Schön, Svenja Voss, Vishnu Dhople, Svenja Warnke, Katharina Scherschel, Benedikt Schrage, Paulus Kirchhof, Stefan Blankenberg, Uwe Völker, Dirk Westermann, Elke Hammer, Diana Lindner
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cytokine cardiac fibroblast TGF-β TNF-α secretome proteome Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/1520083bf736432485ff68dd1b97e5d7
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spelling	oai:doaj.org-article:1520083bf736432485ff68dd1b97e5d72021-11-25T17:54:49ZCytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome10.3390/ijms2222122621422-00671661-6596https://doaj.org/article/1520083bf736432485ff68dd1b97e5d72021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12262https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Fibroblasts contribute to approximately 20% of the non-cardiomyocytic cells in the heart. They play important roles in the myocardial adaption to stretch, inflammation, and other pathophysiological conditions. Fibroblasts are a major source of extracellular matrix (ECM) proteins whose production is regulated by cytokines, such as TNF-α or TGF-β. The resulting myocardial fibrosis is a hallmark of pathological remodeling in dilated cardiomyopathy (DCM). Therefore, in the present study, the secretome and corresponding transcriptome of human cardiac fibroblasts from patients with DCM was investigated under normal conditions and after TNF-α or TGF-β stimulation. Secreted proteins were quantified via mass spectrometry and expression of genes coding for secreted proteins was analyzed via Affymetrix Transcriptome Profiling. Thus, we provide comprehensive proteome and transcriptome data on the human cardiac fibroblast’s secretome. In the secretome of quiescent fibroblasts, 58% of the protein amount belonged to the ECM fraction. Interestingly, cytokines were responsible for 5% of the total protein amount in the secretome and up to 10% in the corresponding transcriptome. Furthermore, cytokine gene expression and secretion were upregulated upon TNF-α stimulation, while collagen secretion levels were elevated after TGF-β treatment. These results suggest that myocardial fibroblasts contribute to pro-fibrotic and to inflammatory processes in response to extracellular stimuli.Hanna BräuningerTilo ThottakaraJacob SchönSvenja VossVishnu DhopleSvenja WarnkeKatharina ScherschelBenedikt SchragePaulus KirchhofStefan BlankenbergUwe VölkerDirk WestermannElke HammerDiana LindnerMDPI AGarticlecytokinecardiac fibroblastTGF-βTNF-αsecretomeproteomeBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12262, p 12262 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cytokine cardiac fibroblast TGF-β TNF-α secretome proteome Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	cytokine cardiac fibroblast TGF-β TNF-α secretome proteome Biology (General) QH301-705.5 Chemistry QD1-999 Hanna Bräuninger Tilo Thottakara Jacob Schön Svenja Voss Vishnu Dhople Svenja Warnke Katharina Scherschel Benedikt Schrage Paulus Kirchhof Stefan Blankenberg Uwe Völker Dirk Westermann Elke Hammer Diana Lindner Cytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome
description	Fibroblasts contribute to approximately 20% of the non-cardiomyocytic cells in the heart. They play important roles in the myocardial adaption to stretch, inflammation, and other pathophysiological conditions. Fibroblasts are a major source of extracellular matrix (ECM) proteins whose production is regulated by cytokines, such as TNF-α or TGF-β. The resulting myocardial fibrosis is a hallmark of pathological remodeling in dilated cardiomyopathy (DCM). Therefore, in the present study, the secretome and corresponding transcriptome of human cardiac fibroblasts from patients with DCM was investigated under normal conditions and after TNF-α or TGF-β stimulation. Secreted proteins were quantified via mass spectrometry and expression of genes coding for secreted proteins was analyzed via Affymetrix Transcriptome Profiling. Thus, we provide comprehensive proteome and transcriptome data on the human cardiac fibroblast’s secretome. In the secretome of quiescent fibroblasts, 58% of the protein amount belonged to the ECM fraction. Interestingly, cytokines were responsible for 5% of the total protein amount in the secretome and up to 10% in the corresponding transcriptome. Furthermore, cytokine gene expression and secretion were upregulated upon TNF-α stimulation, while collagen secretion levels were elevated after TGF-β treatment. These results suggest that myocardial fibroblasts contribute to pro-fibrotic and to inflammatory processes in response to extracellular stimuli.
format	article
author	Hanna Bräuninger Tilo Thottakara Jacob Schön Svenja Voss Vishnu Dhople Svenja Warnke Katharina Scherschel Benedikt Schrage Paulus Kirchhof Stefan Blankenberg Uwe Völker Dirk Westermann Elke Hammer Diana Lindner
author_facet	Hanna Bräuninger Tilo Thottakara Jacob Schön Svenja Voss Vishnu Dhople Svenja Warnke Katharina Scherschel Benedikt Schrage Paulus Kirchhof Stefan Blankenberg Uwe Völker Dirk Westermann Elke Hammer Diana Lindner
author_sort	Hanna Bräuninger
title	Cytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome
title_short	Cytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome
title_full	Cytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome
title_fullStr	Cytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome
title_full_unstemmed	Cytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome
title_sort	cytokine-mediated alterations of human cardiac fibroblast’s secretome
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1520083bf736432485ff68dd1b97e5d7
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Cytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome

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