A5063360982- Systemic Sclerosis and Related Diseases
- Dermatologic Treatments and Research
- Connective Tissue Growth Factor Research
- Mast cells and histamine
- Phenomenology and Existential Philosophy
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Wnt/β-catenin signaling in development and cancer
- Philosophy and Historical Thought
- Philosophy and Theoretical Science
- Fibroblast Growth Factor Research
- Hedgehog Signaling Pathway Studies
- Philosophy, Science, and History
- Autoimmune Bullous Skin Diseases
- Osteoarthritis Treatment and Mechanisms
- Eosinophilic Disorders and Syndromes
- Bone Metabolism and Diseases
- Dupuytren's Contracture and Treatments
- Electromagnetic Fields and Biological Effects
- Inflammatory mediators and NSAID effects
- Vasculitis and related conditions
- Philosophy, Ethics, and Existentialism
- Rheumatoid Arthritis Research and Therapies
- Kantian Philosophy and Modern Interpretations
- Magnetic and Electromagnetic Effects
- Urticaria and Related Conditions
Universitätsmedizin Göttingen
2022
TU Bergakademie Freiberg
2003-2021
Friedrich-Alexander-Universität Erlangen-Nürnberg
2010-2020
The University of Texas Southwestern Medical Center
2020
Southwestern Medical Center
2020
Universitätsklinikum Erlangen
2014-2019
Torghatten (Norway)
2019
UiT The Arctic University of Norway
2019
University of Göttingen
2017-2018
Kiel University
2017
The transforming growth factor-β (TGF-β) signalling pathway is a key mediator of fibroblast activation that drives the aberrant synthesis extracellular matrix in fibrotic diseases. Here we demonstrate novel link between and canonical Wnt pathway. TGF-β stimulates p38-dependent manner by decreasing expression antagonist Dickkopf-1. Tissue samples from human diseases show enhanced proteins decreased Activation fibroblasts vitro induces fibrosis vivo. Transgenic overexpression Dickkopf-1...
<h3>Objectives</h3> Autophagy is a homeostatic process to recycle dispensable and damaged cell organelles. Dysregulation of autophagic pathways has recently been implicated in the pathogenesis various diseases. Here, we investigated role autophagy during joint destruction arthritis. <h3>Methods</h3> osteoclasts was analysed vitro ex vivo by transmission electron microscopy, Western blotting immunohistochemistry for Beclin1 Atg7. Small molecule inhibitors, LysMCre-mediated knockout Atg7...
Vascular damage and platelet activation are associated with tissue remodeling in diseases such as systemic sclerosis, but the molecular mechanisms underlying this association have not been identified. In study, we show that serotonin (5-hydroxytryptamine [5-HT]) stored platelets strongly induces extracellular matrix synthesis interstitial fibroblasts via of 5-HT2B receptors (5-HT2B) a transforming growth factor β (TGF-β)–dependent manner. Dermal fibrosis was reduced 5-HT2B−/− mice using both...
Objectives Pathologic fibroblast activation drives fibrosis of the skin and internal organs in patients with systemic sclerosis (SSc). β-catenin is an integral part adherens junctions a central component canonical Wnt signaling. Here, authors addressed role fibroblasts for development SSc dermal fibrosis. Methods Nuclear accumulation was assessed by triple staining β-catenin, prolyl-4-hydroxylase-β 4′,6-diamidino-2-phenylindole (DAPI). The expression proteins analysed real-time PCR...
<h3>Objectives</h3> Activated Wnt signalling with decreased expression of endogenous inhibitors has recently been characterised as a central pathomechanism in systemic sclerosis (SSc). Aberrant epigenetic modifications also contribute to the persistent activation SSc fibroblasts. We investigated whether increased and changes are causally linked via promoter hypermethylation-induced silencing antagonists. <h3>Methods</h3> The methylation status antagonists leucocytes fibroblasts was evaluated...
T-helper type 2 responses are crucial in Churg-Strauss syndrome (CSS) and may enhance the production of IgG4 antibodies. The authors assessed immune response CSS patients.The included 46 consecutive patients with (24 active 22 quiescent disease), 26 granulomatosis polyangiitis (GPA, Wegener's), 25 atopic asthma 20 healthy controls determined serum IgG, IgM, IgA, IgE IgG subclass levels. Tissue infiltration by plasma cells was nine CSS, 10 GPA, chronic sinusitis (11 11 without...
Nintedanib is a tyrosine kinase inhibitor that has recently been shown to slow disease progression in idiopathic pulmonary fibrosis two replicate phase III clinical trials. The aim of this study was analyse the antifibrotic effects nintedanib preclinical models systemic sclerosis (SSc) and provide scientific background for trials SSc.The on migration, proliferation, myofibroblast differentiation release extracellular matrix dermal fibroblasts were analysed by microtitre tetrazolium scratch...
Osteoarthritis is the most common form of arthritis and a major socioeconomic burden. Our study first to explore association between serum microRNA levels development severe osteoarthritis knee hip joint in general population.
Nintedanib is an inhibitor targeting platelet-derived growth factor receptor, fibroblast receptor and vascular endothelial tyrosine kinases that has recently been approved for the treatment of idiopathic pulmonary fibrosis. The aim this study was to analyse effects nintedanib in fos-related antigen-2 (Fra2) mouse model systemic sclerosis (SSc).The on arterial hypertension with proliferation smooth muscle cells (PVSMCs) luminal occlusion, microvascular disease apoptosis (MVECs) activation...
<h3>Background</h3> Dermal fibroblasts from patients with systemic sclerosis (SSc) release excessive amounts of collagen resulting in tissue fibrosis. The molecular mechanisms underlying this pathological activation are incompletely understood. <h3>Objective</h3> To investigate whether Notch signalling contributes to the uncontrolled SSc. <h3>Methods</h3> Activation pathway was assessed by immunohistochemistry or Western blot for intracellular domain and ligand Jagged-1 (Jag-1) real-time PCR...
To investigate whether JAK-2 contributes to the pathologic activation of fibroblasts in patients with systemic sclerosis (SSc) and evaluate antifibrotic potential inhibition for treatment SSc.Activation human skin experimental fibrosis was determined by immunohistochemical analysis. signaling inhibited selective inhibitor TG101209 or small interfering RNA. Bleomycin-induced dermal mice TSK-1 were used specific vivo.Increased detected SSc, particularly fibroblasts. The dependent on...
<h3>Background</h3> Vitamin D receptor (VDR) is a member of the nuclear superfamily. Its ligand, 1,25-(OH)<sub>2</sub>D, metabolically active hormone derived from vitamin D<sub>3</sub>. The levels D<sub>3</sub> are decreased in patients with systemic sclerosis (SSc). Here, we aimed to analyse role VDR signalling fibrosis. <h3>Methods</h3> expression was analysed SSc skin, experimental fibrosis and human fibroblasts. modulated by siRNA selective agonist paricalcitol. effects on Smad were...
Tissue fibrosis caused by pathologic activation of fibroblasts with increased synthesis extracellular matrix components is a major hallmark systemic sclerosis (SSc). Notch signaling regulates tissue differentiation, and abnormal has been implicated in the pathogenesis various malignancies. The present study was undertaken to investigate role SSc evaluate therapeutic potential inhibition for treatment fibrosis.Activation pathways analyzed staining intracellular domain (NICD) quantification...
Objectives Autophagy has recently been shown to regulate osteoclast activity and differentiation. Here, we aim investigate the impact of autophagy inhibition as a potential therapeutic approach for treatment osteoporosis in preclinical models. Methods Systemic bone loss was induced mice by glucocorticoids ovariectomy (OVX). targeted conditional inactivation autophagy-related gene 7 (Atg7) with chloroquine (CQ). Bone density evaluated microCT. The role on osteoclastogenesis analysed...
Objectives We have previously described the antifibrotic role of soluble guanylate cyclase (sGC). The mode action, however, remained elusive. In present study, we describe a novel link between sGC signalling and transforming growth factor β (TGFβ) that mediates effects sGC. Methods Human fibroblasts murine knockout were treated with stimulator BAY 41-2272 or stable cyclic guanosine monophosphate (cGMP) analogue 8-Bromo-cGMP stimulated TGFβ. isolated from sGCI fl/fl mice, recombination was...
Abstract Uncontrolled activation of TGFβ signaling is a common denominator fibrotic tissue remodeling. Here we characterize the tyrosine phosphatase SHP2 as molecular checkpoint for TGFβ-induced JAK2/STAT3 and potential target treatment fibrosis. stimulates activity SHP2, although this effect in part counterbalanced by inhibitory effects on expression. Stimulation with promotes recruitment to JAK2 fibroblasts subsequent dephosphorylation at Y570 STAT3. The STAT3 translate into major...
Background and objectives Fibrosis is a major socioeconomic burden, but effective antifibrotic therapies are not available in the clinical routine. There growing evidence for central role of Wnt signalling fibrotic diseases such as systemic sclerosis, we therefore evaluated translational potential pharmacological inhibition experimental dermal fibrosis. Methods We examined effects PKF118-310 ICG-001, two novel inhibitors downstream canonical signalling, models prevention treatment...
Objectives Epigenetic modifications such as DNA methylation and histone acetylation have been implicated in the pathogenesis of systemic sclerosis. However, has not investigated so far. We therefore aimed to evaluate role trimethylation H3 on lysine 27 (H3K27me3) fibroblast activation fibrosis. Methods H3K27me3 was inhibited by 3-deazaneplanocin A (DZNep) cultured fibroblasts two murine models dermal Fibrosis analysed assessment thickening, determination hydroxyproline content quantification...
Glycogen synthase kinase 3β (GSK-3) regulates the phosphorylation and subsequent degradation of β-catenin, thereby preventing aberrant activation canonical Wnt pathway. A study was undertaken to define role GSK-3 in fibroblast experimental models systemic sclerosis (SSc).siRNA specific inhibitors were used inhibit cultured fibroblasts mice. Activation signalling analysed by determining levels nuclear β-catenin measuring mRNA target gene Axin2. The effects on release collagen evaluated human...