TY - THES AU - Bukosza, Éva Nóra TI - A glomeruloszklerózis korai és késői szakaszának vizsgálata rágcsálókban PY - 2021 DO - 10.14753/SE.2021.2448 UR - https://m2.mtmt.hu/api/publication/33644854 ID - 33644854 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Bukosza, Éva Nóra TI - Szemléletváltás küszöbén: új ismereteink a vesefibrosisról krónikus vesebetegségben JF - HYPERTONIA ÉS NEPHROLOGIA J2 - HYPERTONIA NEPHROLOGIA VL - 25 PY - 2021 IS - 2 SP - 53 EP - 60 PG - 8 SN - 1418-477X DO - 10.33668/HN.25.005 UR - https://m2.mtmt.hu/api/publication/32708137 ID - 32708137 AB - A krónikus vesebetegség a sokféle etiológia ellenére végső soron egységesen, a vese fibroticus átalakulási mechanizmusával vezet végstádiumú veseelégtelenséghez. Az elmúlt években született – elsősorban kísérletes – kutatási eredmények jelentősen megváltoztatták az elképzelést a vese ezen átalakulásával kapcsolatban: egyértelművé vált, hogy a vesefibrosis egy dinamikus, sok szereplő részvételével zajló aktív folyamat. Ezen folyamatokban részt vevő tényezők befolyásolása reményt jelenthet arra nézve, hogy képesek leszünk a krónikus vesebetegség végstádiumának megelőzésére. Ez az összefoglaló közlemény a vesefibrosis és a krónikus vesebetegség összefüggését, az elterjedt vizsgálómódszerekből származó eredményeket és a közelmúltban felismert paradigmaváltást hozó tényezőket mutatja be. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Róka, Beáta AU - Tod, Pál AU - Kaucsár, Tamás AU - Bukosza, Éva Nóra AU - Vörös, Imre AU - Varga, Zoltán AU - Petrovich, Balázs AU - Ágg, Bence AU - Ferdinandy, Péter AU - Szénási, Gábor AU - Hamar, Péter TI - Delayed Contralateral Nephrectomy Halted Post-Ischemic Renal Fibrosis Progression and Inhibited the Ischemia-Induced Fibromir Upregulation in Mice JF - BIOMEDICINES J2 - BIOMEDICINES VL - 9 PY - 2021 IS - 7 PG - 19 SN - 2227-9059 DO - 10.3390/biomedicines9070815 UR - https://m2.mtmt.hu/api/publication/32122064 ID - 32122064 N1 - * Megosztott szerzőség LA - English DB - MTMT ER - TY - JOUR AU - Tod, Pál AU - Bukosza, Éva Nóra AU - Róka, Beáta AU - Kaucsár, Tamás AU - Fintha, Attila AU - Krenács, Tibor AU - Szénási, Gábor AU - Hamar, Péter TI - Post-Ischemic Renal Fibrosis Progression Is Halted by Delayed Contralateral Nephrectomy : The Involvement of Macrophage Activation JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 21 PY - 2020 IS - 11 PG - 18 SN - 1661-6596 DO - 10.3390/ijms21113825 UR - https://m2.mtmt.hu/api/publication/31332871 ID - 31332871 AB - (1) Background: Successful treatment of acute kidney injury (AKI)-induced chronic kidney disease (CKD) is unresolved. We aimed to characterize the time-course of changes after contralateral nephrectomy (Nx) in a model of unilateral ischemic AKI-induced CKD with good translational utility. (2) Methods: Severe (30 min) left renal ischemia-reperfusion injury (IRI) or sham operation (S) was performed in male Naval Medical Research Institute (NMRI) mice followed by Nx or S one week later. Expression of proinflammatory, oxidative stress, injury and fibrotic markers was evaluated by RT-qPCR. (3) Results: Upon Nx, the injured kidney hardly functioned for three days, but it gradually regained function until day 14 to 21, as demonstrated by the plasma urea. Functional recovery led to a drastic reduction in inflammatory infiltration by macrophages and by decreases in macrophage chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) mRNA and most injury markers. However, without Nx, a marked upregulation of proinflammatory (TNF-α, IL-6, MCP-1 and complement-3 (C3)); oxidative stress (nuclear factor erythroid 2-related factor 2, NRF2) and fibrosis (collagen-1a1 (Col1a1) and fibronectin-1 (FN1)) genes perpetuated, and the injured kidney became completely fibrotic. Contralateral Nx delayed the development of renal failure up to 20 weeks. (4) Conclusion: Our results suggest that macrophage activation is involved in postischemic renal fibrosis, and it is drastically suppressed by contralateral nephrectomy ameliorating progression. LA - English DB - MTMT ER - TY - JOUR AU - Bukosza, Éva Nóra AU - Kratochwill, Klaus AU - Kornauth, Christoph AU - Schachner, Helga AU - Aufricht, Christoph AU - Gebeshuber, Christoph A. TI - Podocyte RNA sequencing reveals Wnt- and ECM-associated genes as central in FSGS JF - PLOS ONE J2 - PLOS ONE VL - 15 PY - 2020 IS - 4 PG - 13 SN - 1932-6203 DO - 10.1371/journal.pone.0231898 UR - https://m2.mtmt.hu/api/publication/31291830 ID - 31291830 N1 - These authors contributed equally to this work. LA - English DB - MTMT ER - TY - JOUR AU - Bukosza, Éva Nóra AU - Kornauth, Christoph AU - Hummel, Karin AU - Schachner, Helga AU - Huttary, Nicole AU - Krieger, Sigurd AU - Nöbauer, Katharina AU - Oszwald, André AU - Razzazi Fazeli, Ebrahim AU - Kratochwill, Klaus AU - Aufricht, Christoph AU - Szénási, Gábor AU - Hamar, Péter AU - Gebeshuber, Christoph A TI - ECM Characterization Reveals a Massive Activation of Acute Phase Response during FSGS. JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 21 PY - 2020 IS - 6 PG - 13 SN - 1661-6596 DO - 10.3390/ijms21062095 UR - https://m2.mtmt.hu/api/publication/31257752 ID - 31257752 AB - The glomerular basement membrane (GBM) and extra-cellular matrix (ECM) are essential to maintain a functional interaction between the glomerular podocytes and the fenestrated endothelial cells in the formation of the slit diaphragm for the filtration of blood. Dysregulation of ECM homeostasis can cause Focal segmental glomerulosclerosis (FSGS). Despite this central role, alterations in ECM composition during FSGS have not been analyzed in detail yet. Here, we characterized the ECM proteome changes in miR-193a-overexpressing mice, which suffer from FSGS due to suppression of Wilms' tumor 1 (WT1). By mass spectrometry we identified a massive activation of the acute phase response, especially the complement and fibrinogen pathways. Several protease inhibitors (ITIH1, SERPINA1, SERPINA3) were also strongly increased. Complementary analysis of RNA expression data from both miR-193a mice and human FSGS patients identified additional candidate genes also mainly involved in the acute phase response. In total, we identified more than 60 dysregulated, ECM-associated genes with potential relevance for FSGS progression. Our comprehensive analysis of a murine FSGS model and translational comparison with human data offers novel targets for FSGS therapy. LA - English DB - MTMT ER - TY - JOUR AU - Boehm, Michael AU - Bukosza, Éva Nóra AU - Huttary, Nicole AU - Herzog, Rebecca AU - Aufricht, Christoph AU - Kratochwill, Klaus AU - Gebeshuber, Christoph A. TI - A systems pharmacology workflow with experimental validation to assess the potential of anakinra for treatment of focal and segmental glomerulosclerosis JF - PLOS ONE J2 - PLOS ONE VL - 14 PY - 2019 IS - 3 PG - 11 SN - 1932-6203 DO - 10.1371/journal.pone.0214332 UR - https://m2.mtmt.hu/api/publication/31055164 ID - 31055164 AB - Focal and Segmental Glomerulosclerosis (FSGS) is a severe glomerulopathy that frequently leads to end stage renal disease. Only a subset of patients responds to current therapies, making it important to identify alternative therapeutic options. The interleukin (IL)-1 receptor antagonist anakinra is beneficial in several diseases with renal involvement. Here, we evaluated the potential of anakinra for FSGS treatment. Molecular process models obtained from scientific literature data were used to build FSGS pathology and anakinra mechanism of action models by exploiting information on protein interactions. These molecular models were compared by statistical interference analysis and expert based molecular signature matching. Experimental validation was performed in Adriamycin- and lipopolysaccharide (LPS)-induced nephropathy mouse models. Interference analysis (containing 225 protein coding genes and 8 molecular process segments) of the FSGS molecular pathophysiology model with the drug mechanism of action of anakinra identified a statistically significant overlap with 43 shared molecular features that were enriched in pathways relevant in FSGS, such as plasminogen activating cascade, inflammation and apoptosis. Expert adjudication of molecular signature matching, focusing on molecular process segments did not suggest a high therapeutic potential of anakinra in FSGS. In line with this, experimental validation did not result in altered proteinuria or significant changes in expression of the FSGS-relevant genes COL1A1 and NPHS1. In summary, an integrated bioinformatic and experimental workflow showed that FSGS relevant molecular processes can be significantly affected by anakinra beyond the direct drug target IL-1 receptor type 1 (IL1R1) context but might not counteract central pathophysiology processes in FSGS. Anakinra is therefore not suggested for extended preclinical trials. LA - English DB - MTMT ER - TY - JOUR AU - Bukosza, Éva Nóra AU - Kaucsár, Tamás AU - Godó, Mária AU - Lajtár, Enikő AU - Tod, Pál AU - Koncsos, Gábor AU - Varga, Zoltán AU - Baranyai, Tamás AU - Nguyen, Minh Tu AU - Schachner, Helga AU - Sőti, Csaba AU - Ferdinandy, Péter AU - Giricz, Zoltán AU - Szénási, Gábor AU - Hamar, Péter TI - Glomerular Collagen Deposition and Lipocalin-2 Expression Are Early Signs of Renal Injury in Prediabetic Obese Rats JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 20 PY - 2019 IS - 17 PG - 17 SN - 1661-6596 DO - 10.3390/ijms20174266 UR - https://m2.mtmt.hu/api/publication/30789521 ID - 30789521 N1 - * Megosztott szerzőség AB - Feeding rats with high-fat diet (HFD) with a single streptozotocin (STZ) injection induced obesity, slightly elevated fasting blood glucose and impaired glucose and insulin tolerance, and caused cardiac hypertrophy and mild diastolic dysfunction as published before by Koncsos et al. in 2016. Here we aimed to explore the renal consequences in the same groups of rats. Male Long-Evans rats were fed normal chow (CON; n = 9) or HFD containing 40% lard and were administered STZ at 20 mg/kg (i.p.) at week four (prediabetic rats, PRED, n = 9). At week 21 blood and urine samples were taken and kidney and liver samples were collected for histology, immunohistochemistry and for analysis of gene expression. HFD and STZ increased body weight and visceral adiposity and plasma leptin concentration. Despite hyperleptinemia, plasma C-reactive protein concentration decreased in PRED rats. Immunohistochemistry revealed elevated collagen IV protein expression in the glomeruli, and Lcn2 mRNA expression increased, while Il-1β mRNA expression decreased in both the renal cortex and medulla in PRED vs. CON rats. Kidney histology, urinary protein excretion, plasma creatinine, glomerular Feret diameter, desmin protein expression, and cortical and medullary mRNA expression of TGF-β1, Nrf2, and PPARγ were similar in CON and PRED rats. Reduced AMPKα phosphorylation of the autophagy regulator Akt was the first sign of liver damage, while plasma lipid and liver enzyme concentrations were similar. In conclusion, glomerular collagen deposition and increased lipocalin-2 expression were the early signs of kidney injury, while most biomarkers of inflammation, oxidative stress and fibrosis were negative in the kidneys of obese, prediabetic rats with mild heart and liver injury. LA - English DB - MTMT ER - TY - JOUR AU - Bukosza, Éva Nóra AU - Kaucsár, Tamás AU - Godó, Mária AU - Lajtár, Enikő AU - Tod, Pál AU - Koncsos, Gábor AU - Varga, Zoltán AU - Nguyen, Minhtu AU - Schachner, Helga AU - Sőti, Csaba AU - Giricz, Zoltán AU - Szénási, Gábor AU - Hamar, Péter TI - THE KIDNEY IS RELATIVELY RESISTANT TO OBESITY-RELATED COMORBIDITY IN PREDIABETIC LONG EVANS RATS FED A HIGH FAT DIET JF - NEPHROLOGY DIALYSIS TRANSPLANTATION J2 - NEPHROL DIAL TRANSPL VL - 34 PY - 2019 IS - Suppl. 1 SN - 0931-0509 DO - 10.1093/ndt/gfz106.FP059 UR - https://m2.mtmt.hu/api/publication/30724853 ID - 30724853 AB - INTRODUCTION: We have shown previously that rats fed high fat diet with a single STZ injection developed obesity, prediabetes, cardiac hypertrophy, diastolic dysfunction and mild liver damage (Koncsos et al., 2016, Am J Physiol Heart Circ Physiol 311(4):H927-H943). The current study aimed to explore the renal consequences in the same groups of rats.METHODS: Male Long-Evans rats were fed normal chow (control; CON; n=9) or high-fat diet containing 40% lard and were administered streptozotocin (20 mg/kg, i.p.) at week four (prediabetic rats; PRED, n=9). At week 21 cardiac function was examined and blood and urine samples were collected for measuring urinary protein concentration, and serum urea, creatinine and leptin concentrations. Kidney samples were collected for histology, immunohistochemistry and mRNA expression. LA - English DB - MTMT ER - TY - JOUR AU - Brown, Markus AU - Johnson, Louise A AU - Leone, Dario A AU - Majek, Peter AU - Vaahtomeri, Kari AU - Senfter, Daniel AU - Bukosza, Éva Nóra AU - Schachner, Helga AU - Asfour, Gabriele AU - Langer, Brigitte AU - Hauschild, Robert AU - Parapatics, Katja AU - Hong, Young-Kwon AU - Bennett, Keiryn L AU - Kain, Renate AU - Detmar, Michael AU - Sixt, Michael AU - Jackson, David G AU - Kerjaschki, Dontscho TI - Lymphatic exosomes promote dendritic cell migration along guidance cues JF - JOURNAL OF CELL BIOLOGY J2 - J CELL BIOL VL - 217 PY - 2018 IS - 6 SP - 2205 EP - 2221 PG - 17 SN - 0021-9525 DO - 10.1083/jcb.201612051 UR - https://m2.mtmt.hu/api/publication/27589080 ID - 27589080 N1 - \n Clinical Department of Pathology, Medical University of Vienna, Vienna, Austria \n Institute of Science and Technology, Klosterneuburg, Austria \n Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, England, United Kingdom \n CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria \n Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria \n Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United States \n Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland \n Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland \n Cited By :3 \n Export Date: 27 November 2018 \n CODEN: JCLBA \n Correspondence Address: Kerjaschki, D.; Clinical Department of Pathology, Medical University of ViennaAustria; email: Dontscho.kerjaschki@meduniwien.ac.at \n Chemicals/CAS: fractalkine, 199619-66-4 \n Funding details: Austrian Science Fund, FWF \n Funding details: 668036 \n Funding details: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNSF \n Funding details: Academy of Finland, 287853 \n Funding details: Österreichischen Akademie der Wissenschaften, ÖAW \n Funding details: European Research Council, ERC, ERC GA 281556 \n Funding details: MC_UU_12010/2 \n Funding details: Medical Research Council, MRC, MR/L008610/1 \n Funding details: Medical Research Council, MRC, G1100134 \n Funding text 1: M. Brown was supported by the Cell Communication in Health and Disease Graduate Study Program of the Austrian Science Fund and Medizinische Universität Wien, M. Sixt by the European Research Council (ERC GA 281556) and an Austrian Science Fund START award, K.L. Bennett by the Austrian Academy of Sciences, D.G. Jackson and L.A. Johnson by Unit Funding (MC_UU_12010/2) and project grants from the Medical Research Council (G1100134 and MR/L008610/1), and M. Detmar by the Schweizerischer Nationalfonds zur Förderung der Wissenschaft-lichen Forschung and Advanced European Research Council grant LYVICAM. K. Vaahtomeri was supported by an Academy of Finland postdoctoral research grant (287853). This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 668036 (RELENT). The authors declare no competing financial interests. Funding Agency and Grant Number: Cell Communication in Health and Disease Graduate Study Program of the Austrian Science Fund; Medizinische Universitat Wien; European Research Council (ERC)European Research Council (ERC) [GA 281556]; Austrian Science Fund START award; Austrian Academy of Sciences; Medical Research CouncilMedical Research Council UK (MRC) [G1100134, MR/L008610/1]; Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen ForschungAustrian Science Fund (FWF); Advanced European Research Council grant LYVICAM; Academy of FinlandAcademy of Finland [287853]; European UnionEuropean Union (EU) [668036]; [MC_UU_12010/2] Funding text: M. Brown was supported by the Cell Communication in Health and Disease Graduate Study Program of the Austrian Science Fund and Medizinische Universitat Wien, M. Sixt by the European Research Council (ERC GA 281556) and an Austrian Science Fund START award, K.L. Bennett by the Austrian Academy of Sciences, D.G. Jackson and L.A. Johnson by Unit Funding (MC_UU_12010/2) and project grants from the Medical Research Council (G1100134 and MR/L008610/1), and M. Detmar by the Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung and Advanced European Research Council grant LYVICAM. K. Vaahtomeri was supported by an Academy of Finland postdoctoral research grant (287853). This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 668036 (RELENT). Clinical Department of Pathology, Medical University of Vienna, Vienna, Austria Institute of Science and Technology, Klosterneuburg, Austria Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, England, United Kingdom CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United States Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland Cited By :12 Export Date: 3 March 2020 CODEN: JCLBA Correspondence Address: Kerjaschki, D.; Clinical Department of Pathology, Medical University of ViennaAustria; email: Dontscho.kerjaschki@meduniwien.ac.at Chemicals/CAS: fractalkine, 199619-66-4; collagen, 9007-34-5; Chemokine CX3CL1; Collagen; CX3CL1 protein, human; Receptors, G-Protein-Coupled; Tumor Necrosis Factor-alpha Funding details: Medizinische Universität Wien Funding details: Academy of Finland, 287853 Funding details: Austrian Science Fund, FWF Funding details: Ãsterreichischen Akademie der Wissenschaften, ÃAW, MC_UU_12010/2 Funding details: European Research Council, ERC Funding details: European Research Council, ERC, GA 281556 Funding details: Medical Research Council, MRC, MR/L008610/1, G1100134 Funding details: 668036 Funding text 1: M. Brown was supported by the Cell Communication in Health and Disease Graduate Study Program of the Austrian Science Fund and Medizinische Universität Wien, M. Sixt by the European Research Council (ERC GA 281556) and an Austrian Science Fund START award, K.L. Bennett by the Austrian Academy of Sciences, D.G. Jackson and L.A. Johnson by Unit Funding (MC_UU_12010/2) and project grants from the Medical Research Council (G1100134 and MR/L008610/1), and M. Detmar by the Schweizerischer Nationalfonds zur Förderung der Wissenschaft-lichen Forschung and Advanced European Research Council grant LYVICAM. K. Vaahtomeri was supported by an Academy of Finland postdoctoral research grant (287853). This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 668036 (RELENT). The authors declare no competing financial interests. AB - Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified > 1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments. © 2018 Brown et al. LA - English DB - MTMT ER -