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, Jahrgang 22, Nr. 22, 12262, 12.11.2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -