A5014631735- Platelet Disorders and Treatments
- Liver physiology and pathology
- Cell Adhesion Molecules Research
- Blood properties and coagulation
- Liver Disease Diagnosis and Treatment
- Pancreatic function and diabetes
- Antiplatelet Therapy and Cardiovascular Diseases
- Pediatric Hepatobiliary Diseases and Treatments
- Advanced Proteomics Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Polymer Surface Interaction Studies
- Inflammatory Biomarkers in Disease Prognosis
- Macrophage Migration Inhibitory Factor
- Cellular Mechanics and Interactions
- Heparin-Induced Thrombocytopenia and Thrombosis
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Blood Coagulation and Thrombosis Mechanisms
- Genetic and Kidney Cyst Diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Electrospun Nanofibers in Biomedical Applications
- thermodynamics and calorimetric analyses
- Drug Solubulity and Delivery Systems
- Protease and Inhibitor Mechanisms
- Caveolin-1 and cellular processes
- Hemophilia Treatment and Research
Institute of Molecular Genetics
2019-2025
Czech Academy of Sciences, Institute of Molecular Genetics
2012-2024
Czech Academy of Sciences
2024
Rockefeller University
2003-2009
Center for Vascular Biology Research
2007
University of Cincinnati
2004
Icahn School of Medicine at Mount Sinai
1999-2003
Cincinnati Children's Hospital Medical Center
2003
Institute of Haematology and Blood Transfusion
1997-2000
Charles University
1997
The leukocyte integrin alpha(M)beta(2)/Mac-1 appears to support the inflammatory response through multiple ligands, but local engagement of fibrin(ogen) may be particularly important for function. To define biological significance fibrin(ogen)-alpha(M)beta(2) interaction in vivo, gene-targeted mice were generated which alpha(M)beta(2)-binding motif within fibrinogen gamma chain (N(390)RLSIGE(396)) was converted a series alanine residues. Mice carrying Fibgamma(390-396A) allele maintained...
Accumulation of extracellular matrix (ECM) in liver fibrosis is associated with changes protein abundance and composition depending upon etiology the underlying disease. Current efforts to unravel etiology-specific mechanisms pharmacological targets rely on several models experimental fibrosis. Here, we characterize compare dynamics hepatic proteome remodeling during development spontaneous healing hepatotoxic (carbon tetrachloride (CCl 4 ) intoxication) cholestatic...
Accumulation of extracellular matrix (ECM) in liver fibrosis is associated with changes protein abundance and composition depending upon etiology the underlying disease. Current efforts to unravel etiology-specific mechanisms pharmacological targets rely on several models experimental fibrosis. Here, we characterize compare dynamics hepatic proteome remodeling during development spontaneous healing mouse hepatotoxic (carbon tetrachloride [CCl 4 ] intoxication) cholestatic...
Abstract Background Ursodeoxycholic acid (UDCA) is used to treat primary biliary cirrhosis, intrahepatic cholestasis, and other cholestatic conditions. Although much has been learned about the molecular basis of disease pathophysiology, our understanding effects UDCA remains unclear. Possibly underlying its cytoprotective, anti-apoptotic, anti-oxidative effects, was reported regulate expression TNFα inflammatory cytokines. However, it not known if this effect involves also modulation ADAM...
Fibrogenic processes instigate fatal chronic diseases leading to organ failure and death. Underlying biological involve induced massive deposition of extracellular matrix (ECM) by aberrant fibroblasts. We subjected diseased primary human lung fibroblasts an advanced three-dimensional phenotypic high-content assay screened a repurposing drug library small molecules for inhibiting ECM deposition. Fibrotic Pattern Detection Artificial Intelligence identified tranilast as effective inhibitor....
The signalling pathway elicited by hepatocyte growth factor (HGF) and its receptor c-Met is indispensable for liver development regeneration. It has been described that released from the cell surface a disintegrin metalloprotease 10 (ADAM10) resulting in soluble form known as sMet. Using human hepatocellular HepG2 hepatic stellate LX2 lines we show sMet of cells both ADAM17 ADAM10, with appearing to be major proteinase. Moreover, using mouse model 3,5-diethoxycarbonyl- 1,4-dihydroxycollidine...
Liver fibrosis is characterized by the deposition and increased turnover of extracellular matrix. This process controlled matrix metalloproteinases (MMPs), whose expression activity dynamically change during injury progression. MMP-19, one most widely expressed MMPs, highly in liver; however, its contribution to liver pathology unknown. The aim this study was elucidate role MMP-19 development resolution comparing response MMP-19-deficient (MMP19KO) wild-type mice upon chronic...
Abstract ADAM10 and ADAM17 are proteases that affect multiple signalling pathways by releasing molecules from the cell surface. As their substrate specificities partially overlaps, we investigated concurrent role in liver regeneration fibrosis, using three liver-specific deficient mouse lines: ADAM10- ADAM17-deficient lines, a line for both proteases. In model of partial hepatectomy, double mice exhibited decreased AKT phosphorylation, release EGFR activating factors lower shedding HGF...
A combination of experimental and computational approaches was used to provide a structural context for the role beta3 integrin subunit ligand-associated metal binding site (LIMBS) in physiological ligands integrins. Specifically, we have carried out (1) adhesion assays on cells expressing normal alphaIIbeta3, alphaVbeta3, or corresponding D217A LIMBS mutants; (2) equilibrium nonequilibrium (steered) molecular dynamics (MD) simulations eptifibatide complex with either fully hydrated...
Matrix stiffening has been recognized as one of the key drivers progression liver fibrosis. It profound effects on various aspects cell behavior such function, differentiation, and motility. However, these processes are not homogeneous throughout whole organ, it become increasingly important to understand changes in mechanical properties tissues cellular level. To be able monitor collagen-rich areas within lobes, this paper presents a protocol for measuring tissue elastic moduli with high...
Platelet fibrin(ogen) adhesive interactions were investigated in whole citrated blood using the rectangular perfusion chamber at wall shear rates of 300 and 1600 s(-1) with regard to amount structure immobilized protein. Only single platelets adhered adsorbed fibrinogen both low high surface concentrations almost no adhesion was observed. When spray-immobilized protein, platelet significantly higher than Conversion fibrin monomer resulted formation pronounced aggregates elevation rate 50%...