A5072715760- Systemic Sclerosis and Related Diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Peptidase Inhibition and Analysis
- Dermatologic Treatments and Research
- Skin and Cellular Biology Research
- Fibroblast Growth Factor Research
- Galectins and Cancer Biology
- Connective Tissue Growth Factor Research
- Bone Metabolism and Diseases
- Glycosylation and Glycoproteins Research
- Wnt/β-catenin signaling in development and cancer
- Dermatological and Skeletal Disorders
- Inflammatory Myopathies and Dermatomyositis
- Cellular Mechanics and Interactions
- Protein Tyrosine Phosphatases
- Lymphatic System and Diseases
- Mesenchymal stem cell research
- Cell Image Analysis Techniques
- Mast cells and histamine
- Cardiac Fibrosis and Remodeling
- Autoimmune Bullous Skin Diseases
- Cardiac Structural Anomalies and Repair
- Protease and Inhibitor Mechanisms
- Chronic Myeloid Leukemia Treatments
- TGF-β signaling in diseases
Heinrich Heine University Düsseldorf
2022-2025
Düsseldorf University Hospital
2022-2025
Universitätsklinikum Erlangen
2018-2024
Friedrich-Alexander-Universität Erlangen-Nürnberg
2018-2024
Carol Davila University of Medicine and Pharmacy
2016
During surgery, rapid and accurate histopathological diagnosis is essential for clinical decision making. Yet the prevalent method of intra-operative consultation pathology intensive in time, labour costs, requires expertise trained pathologists. Here we show that biopsy samples can be analysed within 30 min by sequentially assessing physical phenotypes singularized suspended cells dissociated from tissues. The diagnostic combines enzyme-free mechanical dissociation tissues, real-time...
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...
Objective Expression of dipeptidylpeptidase 4 ( DPP ‐4) identifies a dermal fibroblast lineage involved in scarring during wound healing. The role DDP ‐4 tissue fibrosis is, however, unknown. aim the present study was to evaluate as potential target for treatment patients with systemic sclerosis SS c). Methods skin biopsy samples and fibroblasts analyzed by real‐time polymerase chain reaction, immunofluorescence, Western blot analyses. activity modulated overexpression, knockdown,...
Fibrotic diseases impose a major socioeconomic challenge on modern societies and have limited treatment options. Adropin, peptide hormone encoded by the energy homeostasis–associated ( ENHO ) gene, is implicated in metabolism vascular homeostasis, but its role pathogenesis of fibrosis remains enigmatic. Here, we used machine learning approaches combination with functional vitro vivo experiments to characterize adropin as potential regulator involved fibroblast activation tissue systemic...
Systemic sclerosis (SSc) is a connective tissue disease that can serve as model to study vascular changes in response inflammation, autoimmunity, and fibrotic remodeling. Although microvascular are the earliest histopathologic manifestation of SSc, pathophysiology remains poorly understood.
Systemic sclerosis (SSc) primary heart involvement (SSc-pHI) is one of the leading causes mortality in SSc. We aimed to evaluate risk factors for SSc-pHI and its progression outcomes EUSTAR (European Scleroderma Trials Research) cohort. was defined according World Foundation/Heart Failure Association definition. Data from 5741 patients with SSc cohort were analyzed. Additional cardiovascular data collected a subcohort 838 Lasso regression used factor analyses. Kaplan-Meier estimator survival...
Myocardial fibrosis (MF) is a factor of poor prognosis in systemic sclerosis (SSc). Direct in-vivo visualization fibroblast activation as early readout MF has not been feasible to date. Here, we characterize 68Gallium-labeled-Fibroblast-Activation-Inhibitor-04 ([68Ga]Ga-FAPI-04)-PET-CT diagnostic tool SSc-related MF.In this proof-of-concept trial, six SSc patients with and eight without the EUSTAR cohort Erlangen underwent [68Ga]Ga-FAPI-04-PET-CT cardiac MRI (cMRI) clinical serologic...
Up-regulation of FGFR3 and FGF9 induces profibrotic pathways promoting fibroblast activation tissue fibrosis in systemic sclerosis.
Interstitial lung disease (ILD) is the leading cause of mortality in SSc. Novel biomarkers are crucial to improve outcomes SSc-ILD. We aimed compare performance potential serum SSc-ILD that reflect different pathogenic processes: KL-6 and SP-D (epithelial injury), CCL18 (type 2 immune response), YKL-40 (endothelial injury matrix remodelling) MMP-7 (ECM remodelling).
Stimulators of soluble guanylate cyclase (sGC) are currently investigated in clinical trials for the treatment fibrosis systemic sclerosis (SSc). In this study, we aim to investigate role protein kinases G (PKG) as downstream mediators sGC-cyclic guanosine monophosphate (cGMP) SSc.Mice with combined knockout PKG1 and 2 were challenged bleomycin treated sGC stimulator BAY 41-2272. Fibroblasts 41-2272 PKG inhibitor KT 5823.PKG1 upregulated SSc a transforming growth factor-β1 (TGFβ1)-dependent...
Transforming growth factor-β (TGFβ) is a key mediator of fibroblast activation in fibrotic diseases, including systemic sclerosis. Here we show that Engrailed 1 (EN1) reexpressed multiple subpopulations the skin SSc patients. We characterize EN1 as molecular amplifier TGFβ signaling myofibroblast differentiation: induces expression SMAD3-dependent manner, and turn, mediates profibrotic effects TGFβ. RNA sequencing demonstrates gene profile functionally related to cytoskeleton organization...
Bone mass is maintained by the balance between osteoclast-induced bone resorption and osteoblast-triggered formation. In inflammatory arthritis such as rheumatoid (RA), however, increased osteoclast differentiation activity skew this resulting in progressive loss. O-GlcNAcylation a posttranslational modification with attachment of single O-linked β-D-N-acetylglucosamine (O-GlcNAc) residue to serine or threonine residues target proteins. Although one most common protein modifications, its...
Objectives Transcriptomic data demonstrated that fibroblasts are heterogeneous with functionally diverse subpopulations. Although key effector cells of fibrotic diseases such as systemic sclerosis (SSc), they have not yet been characterised spatially at the cellular level. Here, we aimed to investigate fibroblast subpopulations using imaging mass cytometry (IMC) a proteomic-based, resolved omics approach. Methods We applied IMC deconvolute heterogeneity 49 969 including 6501 single-cell...
Key Points1.The porcupine inhibitor Wnt-C59 ameliorated clinical signs of sclGvHD, reduced inflammation and fibrotic tissue remodeling without significant toxicity both as monotherapy in combination with ruxolitinib, belumosudil or ibrutinib experimental sclGvHD.2. Porcupine inhibition showed synergistic effects preventing the skin sclGvHD.
Systemic sclerosis (SSc) is a prototypical fibrotic disease with high mortality and limited treatment options. Despite advances in single-cell RNA sequencing (scRNA-seq), the comprehensive understanding of cellular heterogeneity cell-cell interaction within fibrogenesis microenvironment remains limited. We generated spatially resolved transcriptome maps from healthy SSc skin built scRNA-seq atlas to map data spatial space. This enabled us identify niche, enriched fibroblasts macrophages,...
Abstract Tissue resident cells undergo metabolic reprogramming during fibrotic tissue remodeling to meet their changing demands required for extracellular matrix production and phenotypic transitions in fibrosis. However, the tissues has not yet been explored at single cell level with spatial resolution. Moreover, organization of niches remains understudied. To address these gaps, we used imaging mass cytometry (IMC) characterized regulome, indicative activity several key pathways systemic...
Objectives Fibrosis is a complex pathophysiological process involving interplay between multiple cell types. Experimental modelling of fibrosis essential for the understanding its pathogenesis and testing putative antifibrotic drugs. However, most current models employ either phylogenetically distant species or rely on human cells cultured in an artificial environment. Here we evaluated potential vascularised vitro skin equivalents as novel model platform evaluation Methods Skin were...
Systemic sclerosis (SSc) is an autoimmune disease that transitions from vasculopathy as initiating pathogenic event to tissue fibrosis. The mechanisms of these remain, however, poorly understood, mainly because complex multicellular human models SSc are lacking. Here we characterized blood vessel organoids (BVOs) a novel model system in SSc. We demonstrate exposure SSc-BVOs serum triggers changes on epigenetic, mRNA and protein levels recapitulates key features vasculopathy, with shifts...
Fibrotic tissues are characterized by excessive crosslinking between extracellular matrix (ECM) proteins, rendering them more resistant to degradation. Although increased of ECM is thought play an important role for progression tissue fibrosis, enhanced has not yet been targeted therapeutically in systemic sclerosis (SSc). Here, we investigated the transglutaminase 2 (TG2), a central enzyme, activation SSc fibroblasts.We assessed TG2 expression and activity using staining, Western blotting,...
Deregulation of the cJUN/AP-1 and hedgehog/GLI2 signaling pathways has been implicated in fibroblast activation systemic sclerosis (SSc). However, consequences their concomitant up-regulation are unknown. Here, we tested hypothesis that mutual amplification both might drive persistent activation.