Key result
TNF-α stimulation upregulated cytokine gene expression and secretion, while TGF-β treatment elevated collagen secretion in human cardiac fibroblasts from patients with dilated cardiomyopathy.
Why the study?
Myocardial fibrosis regulated by cytokines is a hallmark of pathological remodeling in dilated cardiomyopathy, prompting investigation of the secretome and transcriptome of human cardiac fibroblasts.
Human cardiac fibroblasts from DCM patients actively contribute to pro-fibrotic and inflammatory processes in response to extracellular stimuli like TNF-α and TGF-β.
Answers are grounded in this paper and cite their sources.
May implicate fibroblasts in DCM fibrosis; hypothesis-generating and should not yet change practice.
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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Bräuninger et al. (2021) studied Dilated cardiomyopathy (DCM). TNF-α or TGF-β stimulation vs. Normal conditions (quiescent fibroblasts) was evaluated on Secretome and transcriptome alterations. TNF-α stimulation upregulated cytokine gene expression and secretion, while TGF-β treatment elevated collagen secretion in human cardiac fibroblasts from patients with dilated cardiomyopathy.
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