Cytokine-Mediated Alterations of Human Cardiac Fibroblast's Secretome

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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.

In: INT J MOL SCI, Vol. 22, No. 22, 12262, 12.11.2021.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

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Bräuninger H, Thottakara T, Schön J, Voss S, Dhople V, Warnke S et al. Cytokine-Mediated Alterations of Human Cardiac Fibroblast's Secretome. INT J MOL SCI. 2021 Nov 12;22(22). 12262. https://doi.org/10.3390/ijms222212262

Bibtex

@article{8bd69e78711046dcbda24c2b04dcde8c,
title = "Cytokine-Mediated Alterations of Human Cardiac Fibroblast's Secretome",
abstract = "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.",
keywords = "Cardiomyopathy, Dilated/genetics, Cells, Cultured, Collagen/genetics, Cytokines/genetics, Fibroblasts/cytology, Humans, Microscopy, Fluorescence, Myocardium/cytology, Oligonucleotide Array Sequence Analysis, Secretome/drug effects, Tandem Mass Spectrometry, Transcriptome/drug effects, Transforming Growth Factor beta/genetics, Tumor Necrosis Factor-alpha/genetics",
author = "Hanna Br{\"a}uninger and Tilo Thottakara and Jacob Sch{\"o}n and Svenja Voss and Vishnu Dhople and Svenja Warnke and Katharina Scherschel and Benedikt Schrage and Paulus Kirchhof and Stefan Blankenberg and Uwe V{\"o}lker and Dirk Westermann and Elke Hammer and Diana Lindner",
year = "2021",
month = nov,
day = "12",
doi = "10.3390/ijms222212262",
language = "English",
volume = "22",
journal = "INT J MOL SCI",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "22",

}

RIS

TY - JOUR

T1 - Cytokine-Mediated Alterations of Human Cardiac Fibroblast's Secretome

AU - Bräuninger, Hanna

AU - Thottakara, Tilo

AU - Schön, Jacob

AU - Voss, Svenja

AU - Dhople, Vishnu

AU - Warnke, Svenja

AU - Scherschel, Katharina

AU - Schrage, Benedikt

AU - Kirchhof, Paulus

AU - Blankenberg, Stefan

AU - Völker, Uwe

AU - Westermann, Dirk

AU - Hammer, Elke

AU - Lindner, Diana

PY - 2021/11/12

Y1 - 2021/11/12

N2 - 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.

AB - 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.

KW - Cardiomyopathy, Dilated/genetics

KW - Cells, Cultured

KW - Collagen/genetics

KW - Cytokines/genetics

KW - Fibroblasts/cytology

KW - Humans

KW - Microscopy, Fluorescence

KW - Myocardium/cytology

KW - Oligonucleotide Array Sequence Analysis

KW - Secretome/drug effects

KW - Tandem Mass Spectrometry

KW - Transcriptome/drug effects

KW - Transforming Growth Factor beta/genetics

KW - Tumor Necrosis Factor-alpha/genetics

U2 - 10.3390/ijms222212262

DO - 10.3390/ijms222212262

M3 - SCORING: Journal article

C2 - 34830141

VL - 22

JO - INT J MOL SCI

JF - INT J MOL SCI

SN - 1661-6596

IS - 22

M1 - 12262

ER -