Refine
Document Type
- Article (5)
- Doctoral Thesis (2)
Language
- English (7)
Has Fulltext
- yes (7)
Is part of the Bibliography
- no (7)
Keywords
- transcriptome (7) (remove)
Institute
- Abteilung für Mikrobiologie und Molekularbiologie (2)
- Institut für Biometrie und Medizinische Informatik (1)
- Institut für Immunologie u. Transfusionsmedizin - Abteilung Immunologie (1)
- Institut für Pharmazie (1)
- Interfakultäres Institut für Genetik und Funktionelle Genomforschung (UMG) (1)
- Klinik und Poliklinik für Innere Medizin Abt. Nephrologie, Hochdruckkrankheiten und Dialyse (1)
Publisher
- MDPI (3)
- Frontiers Media S.A. (2)
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.
Multidrug-resistant gram-negative pathogens such as Escherichia coli have become increasingly difficult to treat and therefore alternative treatment options are needed. Targeting virulence factors like biofilm formation could be one such option. Inhibition of biofilm-related structures like curli and cellulose formation in E. coli has been shown for different phenolic natural compounds like epigallocatechin gallate. This study demonstrates this effect for other structurally unrelated phenolics, namely octyl gallate, scutellarein and wedelolactone. To verify whether these structurally different compounds influence identical pathways of biofilm formation in E. coli a broad comparative RNA-sequencing approach was chosen with additional RT-qPCR to gain initial insights into the pathways affected at the transcriptomic level. Bioinformatical analysis of the RNA-Seq data was performed using DESeq2, BioCyc and KEGG Mapper. The comparative bioinformatics analysis on the pathways revealed that, irrespective of their structure, all compounds mainly influenced similar biological processes. These pathways included bacterial motility, chemotaxis, biofilm formation as well as metabolic processes like arginine biosynthesis and tricarboxylic acid cycle. Overall, this work provides the first insights into the potential mechanisms of action of novel phenolic biofilm inhibitors and highlights the complex regulatory processes of biofilm formation in E. coli.
Transcriptional Basis for Differential Thermosensitivity of Seedlings of Various Tomato Genotypes
(2020)
Effect of surgical intervention on the activation status of circulating monocytes and T-cells
(2009)
Major surgery causes alterations in immune function which results in immune suppression in post surgical patients. Deactivation of monocytes in these patients is characterised by the reduced ability of these cells to produce pro-inflammatory cytokines on stimulation with LPS in vitro and by markedly reduced HLA-DR expression. Immune suppression in patients with systemic inflammation has also been associated with a high level of apoptosis in both the circulating T and B cell populations. In addition post surgical T cells have a reduced capacity to proliferate ex vivo in response to co-ligation of the T cell receptor and CD-28. Considering these impairments of immune system, this study aimed to define the extent of immune modulation in both innate and adaptive system in a cohort of surgical patients. Measurment of the level of HLA-DR expression of monocytes in these patients showed a considerable change in monocyte phenotype in the immediate post operative period. In line with previous work, all patients showed a considerable reduction in monocytic surface HLA-DR expression which persisted for many hours and those who had post surgical septic complications showed the most severe reduction. Importantly, patients with minor surgical intervention also exhibited decreased HLA-DR expression. Gene expression analysis of monocyte in these patients showed the up-regulated transcripts of genes involved in extravasation and realignment of the cytoskeleton. Analysis of periperal T cell demonstrated a significant reduction in their number in the circulation and a sharp raise in the number of apoptotic T –cells in the immediate post surgical period. Microarray analysis of T cells from patients who developed sepsis and patients with an uneventful recovery within the post-operative period (3 days) showed a substantial reduction in the transcriptional activity of many genes in both groups. However, this down regulation of T cell transcriptional activity appears to be a rather broad and non specific effect since it is not restricted to particular functional pathways. Real time PCR analysis of both the CD4+ and CD8+ populations using selected down-regulated genes showed that the change in transcriptional profile is equally evident both in CD4+ and CD8+ T-cells. The cause of this transient immune depression following surgery remains to be established and it may represent an important enabling factor which contributes to the development of post surgical infections and inflammatory complications.
The Gram-positive bacterium Bacillus licheniformis is an important industrial host for the production of enzymes. Genomic DNA arrays and proteomics are being used to investigate the physiology of this bacterium. A genome-wide transcriptional profiling analysis of the adaptation of B. licheniformis to phosphate starvation shows more than 100 induced genes. Most of strongly induced genes belong to the putative Pho regulon. The data of the transcriptome analysis have been verified by the analysis of the extracellular and cytoplasmic proteome. The main response of B. licheniformis to glucose starvation was a switch to the usage of alternative carbon sources. In addition, B. licheniformis seems to be using other organic substances like amino acids and lipids as carbon sources when subjected to glucose starvation. This was indicated by the induction of a high number of genes the proteins of which are involved in amino acid and lipid degradation. During nitrogen starvation genes necessary for the recruitment of nitrogen from alternative sources were induced, e.g. genes for nitrate and nitrite assimilation, several proteases and peptidases. Both starvation conditions led to a down-regulation of the transcription of most vegetative genes and subsequently to a reduced synthesis of the corresponding proteins. Only a few genes were induced by both starvation conditions like yvyD, citA and the methylcitrate shunt genes mmgD, mmgE and yqiQ. Data of this study use to better understand the physiology of this bacterium during fermentation processes and thus to identify and circumvent bottlenecks of B. licheniformis based bioprocesses. In addition, the phytase promoter was tested for the construction of an alternative phosphate regulated expression system for B. licheniformis.
Aging is an independent risk factor for hypertension, cardiovascular morbidity, and mortality. However, detailed mechanisms linking aging to cardiovascular disease are unclear. We studied the aging effects on the role of perivascular adipose tissue and downstream vasoconstriction targets, voltage-dependent KV7 channels, and their pharmacological modulators (flupirtine, retigabine, QO58, and QO58-lysine) in a murine model. We assessed vascular function of young and old mesenteric arteries in vitro using wire myography and membrane potential measurements with sharp electrodes. We also performed bulk RNA sequencing and quantitative reverse transcription-polymerase chain reaction tests in mesenteric arteries and perivascular adipose tissue to elucidate molecular underpinnings of age-related phenotypes. Results revealed impaired perivascular adipose tissue-mediated control of vascular tone particularly via KV7.3–5 channels with increased age through metabolic and inflammatory processes and release of perivascular adipose tissue-derived relaxation factors. Moreover, QO58 was identified as novel pharmacological vasodilator to activate XE991-sensitive KCNQ channels in old mesenteric arteries. Our data suggest that targeting inflammation and metabolism in perivascular adipose tissue could represent novel approaches to restore vascular function during aging. Furthermore, KV7.3–5 channels represent a promising target in cardiovascular aging.