A5032402107- TGF-β signaling in diseases
- Liver physiology and pathology
- Liver Disease Diagnosis and Treatment
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Tissue Engineering and Regenerative Medicine
- Cancer-related molecular mechanisms research
- Connective Tissue Growth Factor Research
- Mast cells and histamine
- Congenital heart defects research
- Pancreatic and Hepatic Oncology Research
- Mesenchymal stem cell research
- Endoplasmic Reticulum Stress and Disease
- Food Allergy and Anaphylaxis Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Pediatric Hepatobiliary Diseases and Treatments
- Metastasis and carcinoma case studies
- Genetic factors in colorectal cancer
- Organ Transplantation Techniques and Outcomes
- Radiomics and Machine Learning in Medical Imaging
- Pancreatic function and diabetes
- Tracheal and airway disorders
- Polyamine Metabolism and Applications
- Cell Adhesion Molecules Research
- Cancer Research and Treatments
RWTH Aachen University
2016-2025
Universitätsklinikum Aachen
2007-2024
Mast cells (MCs) are a versatile cell type playing key roles in tissue morphogenesis and host defence against bacteria parasites. Furthermore, they can enhance immunological danger signals implicated inflammatory disorders like fibrosis. This granulated originates from the myeloid lineage has similarities to basophilic granulocytes, both containing large quantities of histamine heparin. Immature murine mast mature their destination adopt either connective (CTMC) or mucosal (MMC) type. Some...
Transforming growth factor-β1 (TGF-β1) and BMP-7 (bone morphogenetic protein-7; OP-1) play central, antagonistic roles in kidney fibrosis, a setting which the expression of endoglin (CD105), an accessory TGF-β type III receptor, is increased. So far, known as negative regulator TGF-β/ALK-5 signaling. Here we analyzed effect on TGF-β1 signaling role for both pathways endoglin-deficient L6E9 cells. In this myoblastic cell line, BMPs are opposing cytokines, interfering with myogenic...
The human hepatic cell line LX-2 has been described as tool to study mechanisms of fibrogenesis and the testing antifibrotic compounds. It was originally generated by immortalisation with Simian Vacuolating Virus 40 (SV40) transforming (T) antigen subsequent propagation in low serum conditions. Although this immortalized is used an increasing number studies, detailed genetic characterisation lacking. We here have performed established a single-locus short tandem repeat (STR) profile for...
Hepatic stellate cells (HSCs) play a major role in the pathogenesis of liver fibrosis. Working on primary HSCs requires difficult isolation procedures; therefore we have generated and here characterize mouse hepatic cell line expressing GFP under control collagen 1(I) promoter/enhancer. These are responsive to pro-fibrogenic stimuIi, such as PDGF or TGF-β1, able activate intracellular signalling pathways including Smads MAP kinases. Nevertheless, due basal level activation, TGF-β1 did not...
Regulatory T cells (Treg) play a pivotal role in immune regulation. For proper function, also trace elements such as zinc, and anti-inflammatory cytokines, including transforming growth factor beta 1 (TGF-β1) interleukin (IL)-10 are indispensable. Hence, this study the influence of TGF-β1, IL-10, zinc supplementation on Treg differentiation was investigated.A synergistic effect combined TGF-β1 treatment Foxp3 expression peripheral blood mononuclear mixed lymphocyte cultures (MLC) found by...
Abstract Mast cells develop from the myeloid lineage and are released bone marrow as immature cells, which then differentiate at destination tissue based on cues local environment. In liver, mast recruited in diseased states to fibrogenic surroundings rich TGF-β1. The aim of this study was investigate TGF-β1 signaling primary permanent identify common unique mechanisms. TGF-β receptor repertoire is similar among with high expression type I II receptors very low III (Betaglycan Endoglin)....
Inflammation is a hallmark of cancer. It contributes to heterogeneous, hyperpermeable, and poorly perfused tumor vasculature, as well dense disorganized extracellular matrix, which together negatively affect drug delivery. Reasoning that glucocorticoids have pleiotropic effects, we use clinical-stage dexamethasone liposomes (LipoDex) prime the microenvironment for improved delivery enhanced treatment efficacy. We show LipoDex priming improves vascular function reduces matrix deposition....
The TGF-β signaling pathway is a fundamental in the living cell, which plays key role many central cellular processes. complex and sometimes contradicting mechanisms by yields phenotypic effects are not yet completely understood. In this study we investigated compared transcriptional response profile of TGF-β1 stimulation different cell types. For purpose, extensive experiments performed time-course microarray data generated human mouse parenchymal liver cells, mesenchymal stromal cells...
Abstract The vast majority of colorectal cancer–related deaths can be attributed to metastatic spreading the disease. Therefore, deciphering molecular mechanisms dissemination is a key prerequisite improve future treatment options. With this aim, we took advantage different cancer cell lines and recently established primary cultures enriched in colon stem cells, also known as tumor-initiating cells (TIC), identify genes miRNAs with regulatory functions progression. We show here that...
Extracellular matrix (ECM) is known to maintain epithelial integrity. In carcinogenesis ECM degradation triggers metastasis by controlling migration and differentiation including cancer stem cell (CSC) characteristics. The ECM-modulator inter- α-trypsin inhibitor heavy chain family member five (ITIH5) was recently identified as tumor suppressor potentially involved in impairing breast progression but molecular mechanisms underlying its function are still elusive. ITIH5 expression analyzed...
Lipocalin 2 (LCN2) mediates key roles in innate immune responses. It has affinity for many lipophilic ligands and binds various siderophores, thereby limiting bacterial growth by iron sequestration. Furthermore, LCN2 protects against obesity metabolic syndrome interfering with the composition of gut microbiota. Consequently, complete or hepatocyte-specific ablation Lcn2 gene is associated higher susceptibility to infections. In present study, we comparatively profiled microbiota fecal...
Abstract The molecular mechanisms underlying the transition from nonalcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC) are incompletely understood. During development of NAFLD, Perilipin 5 (PLIN5) can regulate lipid metabolism by suppressing lipolysis and preventing lipotoxicity. Other reports suggest that lack PLIN5 decreases hepatic injury, indicating a protective role in NAFLD pathology. To better understand disease, we established mouse models NAFLD-induced HCC,...
Transforming growth factor β (TGF-β) signaling is mediated by the cell surface TGF-β type I (ALK5), II, and accessory III receptors endoglin betaglycan. Hepatic stellate cells (HSC), most profibrogenic in liver, express ALK5, TβRII, To monitor expression of betaglycan HSC, we used commercially available antibody sc-6199 Western blot analysis. This antibody, raised against a peptide mapping at carboxyl terminus human betaglycan, claimed to be specific for although it known that C-terminal...
Transforming growth factor-beta 1 (TGF-β1) stimulates a broad range of effects which are cell type dependent, and it has been suggested to induce cellular senescence. On the other hand, long-term culture multipotent mesenchymal stromal cells (MSCs) major impact on their physiology therefore is well conceivable that molecular events triggered by TGF-β1 differ considerably in early late passages. In this study, we analyzed effect during replicative senescence MSCs. Stimulation with enhanced...
Immortalized hepatic stellate cells (HSCs) established from mouse, rat, and humans are valuable in vitro models for the biomedical investigation of liver biology. These cell lines homogenous, thereby providing consistent reproducible results. They grow more robustly than primary HSCs provide an unlimited supply proteins or nucleic acids biochemical studies. Moreover, they can overcome ethical concerns associated with use animal human tissue allow fostering 3R principle replacement,...
Liver fibrosis is the outcome of chronic liver injury. Transforming growth factor-β (TGF-β) a major profibrogenic cytokine modulating hepatic stellate cell (HSC) activation and extracellular matrix homeostasis. This study analyses effect Endoglin (Eng), TGF-β type III auxiliary receptor, on fibrogenesis in two models injury by HSC-specific endoglin deletion. Eng expression was measured human murine samples After generating GFAPCre(+) EngΔHSC mice, impact deletion analysed. For vitro...