A5065648186- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Pulmonary Hypertension Research and Treatments
- Systemic Sclerosis and Related Diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Medical Imaging and Pathology Studies
- Inhalation and Respiratory Drug Delivery
- Protease and Inhibitor Mechanisms
- IL-33, ST2, and ILC Pathways
- Metabolomics and Mass Spectrometry Studies
- RNA modifications and cancer
- Lung Cancer Research Studies
- Eosinophilic Esophagitis
- Congenital heart defects research
- Advanced Breast Cancer Therapies
- Occupational and environmental lung diseases
- Peptidase Inhibition and Analysis
- Platelet Disorders and Treatments
- Connective Tissue Growth Factor Research
- Metastasis and carcinoma case studies
- Liver Disease and Transplantation
- Fibroblast Growth Factor Research
- Eicosanoids and Hypertension Pharmacology
- Gout, Hyperuricemia, Uric Acid
- Extracellular vesicles in disease
- Cell Adhesion Molecules Research
Ludwig Boltzmann Institute for Lung Vascular Research
2015-2025
Medical University of Graz
2019-2025
Ludwig Boltzmann Institute for Digital Health and Prevention
2013-2024
Stanford University
2024
Justus-Liebig-Universität Gießen
2024
University of Colorado Denver
2024
Medical University of Vienna
2024
University of Colorado Anschutz Medical Campus
2024
Cardio-Pulmonary Institute
2024
German Center for Lung Research
2024
Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal disease in which the intricate alveolar network of lung progressively replaced by fibrotic scars. Myofibroblasts are effector cells that excessively deposit extracellular matrix proteins thus compromising structure and function. Emerging literature suggests correlation between metabolic alterations IPF. In this study, we show first-line antidiabetic drug metformin exerts potent antifibrotic effects modulating pathways, inhibiting TGFβ1...
Vascular remodelling is a hallmark of pulmonary hypertension (PH) and characterized by enhanced proliferation artery smooth muscle cells (PASMCs). Accumulating evidence indicates crucial role transcription factors in the vascular processes. Here, we characterize involvement meprin β, novel activator protein-1 (AP-1) effector molecule, PH. Fra-2 transgenic (TG) mice exhibited increased right ventricular systolic pressure (RVSP), accompanied activation pro-proliferative pro-fibrotic AKT...
Pulmonary fibrosis is characterized by pronounced collagen deposition and myofibroblast expansion, whose origin plasticity remain elusive. We utilized a fate-mapping approach to investigate α-smooth muscle actin (αSMA)+ platelet-derived growth factor receptor α (PDGFRα)+ cells in two lung models, complemented cell type-specific next-generation sequencing investigations on human lungs. Our data revealed that αSMA+ PDGFRα+ mark distinct mesenchymal lineages with minimal transdifferentiation...
Lung vessel remodeling leads to increased pulmonary vascular resistance, causing arterial hypertension (PAH), and consequently right ventricular hypertrophy failure. In patients suffering from systemic sclerosis (SSc), PAH can occur is a life-threatening complication. Dysregulation of immune processes plays crucial role in remodeling, as has previously been shown Fos-related antigen-2 (Fra-2) transgenic (TG) mice, model SSc-PAH. Here, we investigate whether the Fra-2 TG driven by type 2...
Pulmonary vascular remodeling is a progressive pathological process characterized by functional alterations within pulmonary artery smooth muscle cells (PASMC) and adventitial fibroblasts (PAAF). Mechanisms driving the transition to diseased phenotype remain elusive. Utilizing combination of transcriptomic proteomic profiling, along with phenotyping source-matched from healthy controls individuals idiopathic arterial hypertension (IPAH), our investigation uncovered that while PASMC PAAF...
Background: Pulmonary vascular remodeling is a progressive pathological process characterized by functional alterations within pulmonary artery smooth muscle cells (PASMCs) and adventitial fibroblasts (PAAFs). Mechanisms driving the transition to diseased phenotype remain elusive. Methods: We combined transcriptomic proteomic profiling with phenotypic characterization of source-matched from healthy controls individuals idiopathic arterial hypertension (IPAH). Bidirectional cellular crosstalk...
The interleukin (IL)-1 family of cytokines is strongly associated with systemic sclerosis (SSc) and pulmonary involvement, but the molecular mechanisms are poorly understood. aim this study was to assess role IL-1α IL-1β in vascular interstitial remodelling a mouse model SSc. were localised lungs SSc patients fos-related antigen-2 (Fra-2) transgenic (TG) Lung function, haemodynamic parameters inflammation measured Fra-2 TG mice or without 8 weeks treatment IL-1 receptor antagonist anakinra...
Lung fibrosis is a severe disease characterized by epithelial cell injury, inflammation and collagen deposition. The metalloproteases meprinα meprinβ have been shown to enhance maturation inflammatory infiltration via cleavage of cell-cell contact molecules; therefore we hypothesized that meprins could play role in lung fibrosis. An exhaustive characterization bleomycin-treated meprinα, the double meprinsαβ knock-out (KO) with respective wt-littermates was performed using several different...
The adhesion molecule CD99 is essential for the transendothelial migration of leukocytes. In this study, we used biochemical and cellular assays to show that undergoes ectodomain shedding by metalloprotease meprin β subsequent intramembrane proteolysis γ-secretase. cleavage site in was identified mass spectrometry within an acidic region highly conserved through different vertebrate species. This finding fits perfectly unique specificity with a strong preference aspartate residues suggests...
Background: Asthma is a complex chronic inflammatory disease characterised by airway inflammation, remodelling and hyperresponsiveness (AHR). Members of the AP-1 transcription factor family play important roles in activation immune system control cellular responses; however, their role development asthma has not been well studied. We aimed to investigate lesser known member, Fra2 experimental asthma. Methods: Phenotypic characterisation gene expression profiling was performed on (TG)...
The bleomycin mouse model is the extensively used to study pulmonary fibrosis; however, inflammatory cell kinetics and their compartmentalization still incompletely understood. Here we assembled historical flow cytometry data, totaling 303 samples 16 inflammatory-cell populations, applied advanced data modeling machine learning methods conclusively detail these kinetics.Three days post-bleomycin, profile was typified by acute innate inflammation, pronounced neutrophilia, especially of...
Systemic sclerosis (SSc) is an autoimmune disease characterised by severe vasculopathy and fibrosis of various organs including the lung. Targeted treatment options for SSc-associated interstitial lung (SSc-ILD) are scarce. We assessed effects pirfenidone in a mouse model SSc-ILD.Pulmonary function, inflammation collagen deposition response to were Fra-2-overexpressing transgenic (Fra-2 TG) bleomycin-treated mice. In Fra-2 TG mice, transcriptome was analysed after treatment. vitro, on human...
Summary Pulmonary vascular remodeling is a progressive pathological process characterized by functional alterations within pulmonary artery smooth muscle cells (PASMC) and adventitial fibroblasts (PAAF). Mechanisms driving the transition to diseased phenotype remain elusive. Utilizing combination of transcriptomic proteomic profiling, along with phenotyping source-matched from healthy controls individuals idiopathic arterial hypertension (IPAH), our investigation uncovered that while PASMC...
Abstract Pulmonary arterial hypertension (PAH) is a rare disease characterized by increased pulmonary pressure and vascular remodelling as consequence of smooth muscle cell proliferation, endothelial dysfunction inflammatory infiltrates. Meprin α metalloproteinase whose substrates include adhesion cell–cell contact molecules involved in the process immune extravasation. In this study, we aimed to unravel role meprin PAH-induced remodelling. Our results showed that was present apical membrane...
Abstract Background Pulmonary hypertension (PH) poses a significant health threat with high morbidity and mortality, necessitating improved diagnostic tools for enhanced management. Current biomarkers PH lack functionality comprehensive prognostic capabilities. Therefore, there is critical need to develop that address these gaps in diagnostics prognosis. Methods To this need, we employed metabolomics analysis 233 blood based samples coupled machine learning analysis. For functional insights,...
Pulmonary vascular remodeling is a progressive pathological process characterized by functional alterations within pulmonary artery smooth muscle cells (PASMC) and adventitial fibroblasts (PAAF). Mechanisms driving the transition to diseased phenotype remain elusive. Utilizing combination of transcriptomic proteomic profiling, along with phenotyping source-matched from healthy controls individuals idiopathic arterial hypertension (IPAH), our investigation uncovered that while PASMC PAAF...
Pulmonary vascular remodeling is a progressive pathological process characterized by functional alterations within pulmonary artery smooth muscle cells (PASMC) and adventitial fibroblasts (PAAF). Mechanisms driving the transition to diseased phenotype remain elusive. Utilizing combination of transcriptomic proteomic profiling, along with phenotyping source-matched from healthy controls individuals idiopathic arterial hypertension (IPAH), our investigation uncovered that while PASMC PAAF...