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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: Bräuninger, Hanna, Thottakara, Tilo, Schön, Jacob, Voss, Svenja, Dhople, Vishnu, Warnke, Svenja, Scherschel, Katharina, Schrage, Benedikt, Kirchhof, Paulus, Blankenberg, Stefan, Völker, Uwe, Westermann, Dirk, Hammer, Elke, Lindner, Diana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617966/
https://www.ncbi.nlm.nih.gov/pubmed/34830141
http://dx.doi.org/10.3390/ijms222212262
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author Bräuninger, Hanna
Thottakara, Tilo
Schön, Jacob
Voss, Svenja
Dhople, Vishnu
Warnke, Svenja
Scherschel, Katharina
Schrage, Benedikt
Kirchhof, Paulus
Blankenberg, Stefan
Völker, Uwe
Westermann, Dirk
Hammer, Elke
Lindner, Diana
author_facet Bräuninger, Hanna
Thottakara, Tilo
Schön, Jacob
Voss, Svenja
Dhople, Vishnu
Warnke, Svenja
Scherschel, Katharina
Schrage, Benedikt
Kirchhof, Paulus
Blankenberg, Stefan
Völker, Uwe
Westermann, Dirk
Hammer, Elke
Lindner, Diana
author_sort Bräuninger, Hanna
collection PubMed
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.
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spelling pubmed-86179662021-11-27 Cytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome Bräuninger, Hanna Thottakara, Tilo Schön, Jacob Voss, Svenja Dhople, Vishnu Warnke, Svenja Scherschel, Katharina Schrage, Benedikt Kirchhof, Paulus Blankenberg, Stefan Völker, Uwe Westermann, Dirk Hammer, Elke Lindner, Diana Int J Mol Sci Article 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. MDPI 2021-11-12 /pmc/articles/PMC8617966/ /pubmed/34830141 http://dx.doi.org/10.3390/ijms222212262 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bräuninger, Hanna
Thottakara, Tilo
Schön, Jacob
Voss, Svenja
Dhople, Vishnu
Warnke, Svenja
Scherschel, Katharina
Schrage, Benedikt
Kirchhof, Paulus
Blankenberg, Stefan
Völker, Uwe
Westermann, Dirk
Hammer, Elke
Lindner, Diana
Cytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome
title 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_short Cytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome
title_sort cytokine-mediated alterations of human cardiac fibroblast’s secretome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617966/
https://www.ncbi.nlm.nih.gov/pubmed/34830141
http://dx.doi.org/10.3390/ijms222212262
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