A5066849323- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Autophagy in Disease and Therapy
- Neonatal Respiratory Health Research
- melanin and skin pigmentation
- Inhalation and Respiratory Drug Delivery
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Peptidase Inhibition and Analysis
- Erythrocyte Function and Pathophysiology
- Medical Imaging and Pathology Studies
- Endoplasmic Reticulum Stress and Disease
- Occupational and environmental lung diseases
- Pulmonary Hypertension Research and Treatments
- Cystic Fibrosis Research Advances
- Protease and Inhibitor Mechanisms
- Glycosylation and Glycoproteins Research
- Skin and Cellular Biology Research
- Proteoglycans and glycosaminoglycans research
- Systemic Sclerosis and Related Diseases
- Biochemical Analysis and Sensing Techniques
- Respiratory Support and Mechanisms
- Occupational exposure and asthma
- Mast cells and histamine
- Hops Chemistry and Applications
- Cancer-related molecular mechanisms research
- Neuroscience of respiration and sleep
European Central Bank
2024
Universities of Giessen and Marburg Lung Center
2014-2023
Justus-Liebig-Universität Gießen
2013-2023
German Center for Lung Research
2012-2022
Cardio-Pulmonary Institute
2019-2022
University of Canterbury
2013
The University of Queensland
2013
Universitätsklinikum Gießen und Marburg
2009
Rationale: The molecular pathomechanisms underlying idiopathic pulmonary fibrosis (IPF) are elusive, but chronic epithelial injury has recently been suggested as key event.Objectives: We investigated the possible implication of endoplasmic reticulum (ER) stress–mediated apoptosis in sporadic IPF.Methods: analyzed peripheral explanted lung tissues from patients with IPF (n = 24), obstructive disease (COPD) 9), and organ donors 12) for expression major ER stress mediators markers by means...
<h3>Background</h3> Activation and differentiation of fibroblasts into contractile protein-expressing myofibroblasts their acquired apoptosis-resistant phenotype are critical factors towards the development idiopathic pulmonary fibrosis (IPF), a fatal disease characterised by distorted structure excessive extracellular matrix (ECM) deposition. The molecular mechanisms underlying these processes in IPF remain incompletely understood. We investigated possible implication aberrant...
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Rationale: Although type II alveolar epithelial cells (AEC2s) are chronically injured in idiopathic pulmonary fibrosis (IPF), they contribute to regeneration IPF. Objectives: We hypothesized that Notch signaling may AEC2 proliferation, dedifferentiation characterized by loss of surfactant processing machinery, and lung Methods: applied microarray analysis, kinome profiling, flow cytometry, immunofluorescence western blotting, quantitative PCR, proliferation surface activity analysis study...
The molecular mechanisms underlying Hermansky-Pudlak syndrome-associated interstitial pneumonia (HPSIP) are poorly understood but, as in idiopathic pulmonary fibrosis, may be linked to chronic alveolar epithelial type II cell (AECII) injury.We studied the development of fibrosis and role AECII injury various murine models HPS.HPS1, HPS2, HPS6 monomutant mice, HPS1/2 HPS1/6 double-mutant genetic background were killed at 3 9 months age. Quantitative morphometry was undertaken lung sections...
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease for which no effective therapy exists to date. To identify the molecular mechanisms underlying IPF, we performed comparative proteome analysis of lung tissue from patients with sporadic IPF (n = 14) human donor lungs (controls, n 10) using two-dimensional gel electrophoresis MALDI-TOF-MS. Eighty-nine differentially expressed proteins were identified, 51 up-regulated 38 down-regulated in IPF. Increased expression markers...
Abstract Long noncoding RNAs (lncRNAs) influence the transcription of gene networks in many cell types, but their role tumor‐associated macrophages (TAMs) is still largely unknown. We found that lncRNA ADPGK‐AS1 was substantially upregulated artificially induced M2‐like human macrophages, exposed to lung cancer cells vitro , and TAMs from tissue. partly located within mitochondria binds mitochondrial ribosomal protein MRPL35. Overexpression upregulates tricarboxylic acid cycle promotes...
Among the idiopathic interstitial pneumonias (IIP), two entities IPF and NSIP seem to be clinically related, but has a better outcome. The proteomic signatures which distinguish from remain still elusive. We therefore performed comparative analysis of peripheral lung tissue patients with sporadic (n=14) fibrotic (fNSIP, n=8) organ donors (Controls, n=10), by using 2-dimensional DIGE technique MALDI-TOF-MS. study revealed that profiles fNSIP were quite similar. upregulated proteins in...
Background Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor prognosis. Pirfenidone the first antifibrotic agent to be approved for IPF-treatment as it able slow down progression. However, there no curative treatment other than transplantation. Because epigenetic alterations are associated IPF, histone deacetylase (HDAC)-inhibitors have recently been proven attenuate fibrotic remodeling in vitro and vivo. This study compared effects of pirfenidone pan-HDAC-inhibitor...
Hermansky-Pudlak syndrome (HPS), a hereditary multisystem disorder with oculocutaneous albinism, may be caused by mutations in one of at least 10 separate genes. The HPS-2 subtype is distinguished the presence neutropenia and knowledge its pulmonary phenotype children scarce. Six genetically proven presented to chILD-EU register between 2009 2017; data were collected systematically imaging studies scored blinded. Pulmonary symptoms including dyspnea, coughing, need for oxygen, clubbing...
Amiodarone (AD) is a highly efficient antiarrhythmic drug with potentially serious side effects. Severe pulmonary toxicity reported in patients receiving AD even at low doses and may cause interstitial pneumonia as well lung fibrosis. Apoptosis of alveolar epithelial type II cells (AECII) has been suggested to play an important role this disease. In the current study, we aimed establish murine model AD-induced fibrosis analyze surfactant homeostasis, lysosomal, endoplasmic reticulum (ER)...
Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by type-II alveolar epithelial cell (AECII) injury and fibroblast hyperproliferation. Severe AECII endoplasmic reticulum (ER) stress thought to underlie IPF, but yet incompletely understood. We studied the regulation of C/EBP homologous protein (CHOP), proapoptotic ER-stress-related transcription factor (TF) in AECII-like cells. Interestingly, single or combined overexpression active ER transducers activating factor-4...
Lung cancer is the most common malignancy in humans. Urokinase (uPA) plays a crucial role carcinogenesis by facilitating tumor cell invasion and metastasis.We investigated effect of highly specific urokinase inhibitor CJ-463 (benzylsulfonyl-D-Ser-Ser-4-amidinobenzylamide) on growth, metastasis formation, vascularization murine Lewis lung carcinoma (LLC) human small model.A quantity 3 x 10(6) LLC cells were subcutaneously injected into right flank C57Bl6/N mice, uPA knock out, receptor...
Hemeoxygenase-1 (HO-1), an inducible heat shock protein, is upregulated in response to multiple cellular insults via oxidative stress, lipopolysaccharides (LPS), and hypoxia. In this study, we investigated vitro the role of Toll-like receptor 4 (TLR4), hypoxia-inducible factor 1α (HIF-1α), iron on HO-1 expression cystic fibrosis (CF). Immunohistochemical analysis TLR4, HO-1, ferritin, HIF-1α were performed lung sections CFTR-/- wild-type mice. CFBE41o- 16HBE14o- cell lines employed for...
Chronic injury of alveolar epithelial type II cells (AE2 cells) represents a key event in the development lung fibrosis animal models and humans, such as idiopathic pulmonary (IPF). Intratracheal delivery amiodarone to mice results profound macroautophagy-dependent apoptosis AE2 cells. Increased autophagy manifested by disturbances intracellular surfactant. Hence, we hypothesized that ultrastructural alterations surfactant pool are signs stress correlating with severity fibrotic remodeling....
Endoplasmic reticulum (ER) and mitochondria (mito) play a vital role in alveolar type II cell (AEC2) homeostasis are both stressed patients with idiopathic pulmonary fibrosis (IPF). Up to now, no data available regard ER-mito cross talk tethering under conditions of IPF. We here demonstrate that ER-mitochondrial is reduced upon experimental ER stress vitro the IPF AECII ex vivo, this is-at least part-due decreased phosphofurin acidic cluster sorting protein 2 (PACS-2, also called PACS2)...
Increasing evidence indicates that disequilibrium of the alveolar oxidant–antioxidant balance may play a role in pathogenesis chronic fibrosing lung diseases. Excessive production oxidants and differential regulation antioxidant enzymes have been described under these conditions. We characterized for first time numerous nonenzymatic low-molecular-weight antioxidants bronchoalveolar lavage fluids from patients with different forms fibrosis initiated either by injury to epithelium (idiopathic...
Alveolarization of the developing lung is an important step toward switch from intrauterine life to breathing oxygen-rich air after birth. The distal airways structurally change minimize gas exchange path, and Type II pneumocytes increase production surfactants, which are required reduce surface tension at air-liquid interface in alveolus. Hypoxia-inducible factor 2α (Hif2α) oxygen-regulated transcription expressed endothelial cells, its expression increases end gestation. We investigated...
Abstract Amiodarone (AD) is an iodinated benzofuran derivative, especially known for its antiarrhythmic properties. It exerts serious side‐effects even in patients receiving low doses. AD well‐known to induce apoptosis of type II alveolar epithelial cells (AECII), a mechanism that has been suggested play important role AD‐induced lung fibrosis. The precise molecular mechanisms underlying this disease are, however, still unclear. Because amphiphilic nature, becomes enriched the lysosomal...
Proteases have been shown to degrade airway mucin proteins and damage the epithelium impairing mucociliary clearance. There are increased proteases in COPD but changes protease-antiprotease balance degradation not investigated during course of a exacerbation. We hypothesized that protease levels would lead acute exacerbations. measured neutrophil elastase (NE) alpha 1 inhibitor (A1-PI) using immunoblotting, conducted studies, zymograms, elastin substrate assays cigarette smoke condensate...
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder, and some patients with HPS develop pulmonary fibrosis, known as HPS-associated interstitial pneumonia (HPSIP). We have previously reported that HPSIP associated severe surfactant accumulation, lysosomal stress, alveolar epithelial cell type II (AECII) apoptosis. Here, we hypothesized defective autophagy might result in excessive stress HPSIP. Key proteins, including LC3B lipidation p62, were increased HPS1/2 mice lungs....