TY - JOUR AU - Keszler, Gergely AU - Vékony, Bálint AU - Elek, Zsuzsanna AU - Nemoda, Zsófia AU - Angyal, Nóra AU - Bánlaki, Zsófia AU - Kovács-Nagy, Réka AU - Rónai, Zsolt AU - Réthelyi, János TI - MicroRNA-Mediated Suppression of Glial Cell Line-Derived Neurotrophic Factor Expression Is Modulated by a Schizophrenia-Associated Non-Coding Polymorphism JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 8 PG - 15 SN - 1661-6596 DO - 10.3390/ijms25084477 UR - https://m2.mtmt.hu/api/publication/34804106 ID - 34804106 AB - Plasma levels of glial cell line-derived neurotrophic factor (GDNF), a pivotal regulator of differentiation and survival of dopaminergic neurons, are reportedly decreased in schizophrenia. To explore the involvement of GDNF in the pathogenesis of the disease, a case–control association analysis was performed between five non-coding single nucleotide polymorphisms (SNP) across the GDNF gene and schizophrenia. Of them, the ‘G’ allele of the rs11111 SNP located in the 3′ untranslated region (3′-UTR) of the gene was found to associate with schizophrenia. In silico analysis revealed that the rs11111 ‘G’ allele might create binding sites for three microRNA (miRNA) species. To explore the significance of this polymorphism, transient co-transfection assays were performed in human embryonic kidney 293T (HEK293T) cells with a luciferase reporter construct harboring either the ‘A’ or ‘G’ allele of the 3′-UTR of GDNF in combination with the hsa-miR-1185-1-3p pre-miRNA. It was demonstrated that in the presence of the rs11111 ‘G’ (but not the ‘A’) allele, hsa-miR-1185-2-3p repressed luciferase activity in a dose-dependent manner. Deletion of the miRNA binding site or its substitution with the complementary sequence abrogated the modulatory effect. Our results imply that the rs11111 ‘G’ allele occurring more frequently in patients with schizophrenia might downregulate GDNF expression in a miRNA-dependent fashion. LA - English DB - MTMT ER - TY - JOUR AU - Elek, Zsuzsanna AU - Losoncz, Eszter AU - Fülep, Z. AU - Kovács-Nagy, Réka AU - Bánlaki, Zsófia AU - Szlobodnyik, G. AU - Keszler, Gergely AU - Rónai, Zsolt TI - Persistent sepsis-induced transcriptomic signatures in signaling pathways of peripheral blood leukocytes: A pilot study JF - HUMAN IMMUNOLOGY J2 - HUM IMMUNOL VL - 84 PY - 2023 IS - 11 SP - 600 EP - 608 PG - 9 SN - 0198-8859 DO - 10.1016/j.humimm.2023.08.146 UR - https://m2.mtmt.hu/api/publication/34154205 ID - 34154205 LA - English DB - MTMT ER - TY - JOUR AU - Molnár, Zsuzsanna AU - Losoncz, Eszter AU - Maricza, Katalin AU - Fülep, Z. AU - Bánlaki, Zsófia AU - Kovács-Nagy, Réka AU - Keszler, Gergely AU - Rónai, Zsolt TI - Missense Variants of von Willebrand Factor in the Background of COVID-19 Associated Coagulopathy JF - GENES J2 - GENES-BASEL VL - 14 PY - 2023 IS - 3 PG - 16 SN - 2073-4425 DO - 10.3390/genes14030617 UR - https://m2.mtmt.hu/api/publication/33734164 ID - 33734164 AB - COVID-19 associated coagulopathy (CAC), characterized by endothelial dysfunction and hypercoagulability, evokes pulmonary immunothrombosis in advanced COVID-19 cases. Elevated von Willebrand factor (vWF) levels and reduced activities of the ADAMTS13 protease are common in CAC. Here, we aimed to determine whether common genetic variants of these proteins might be associated with COVID-19 severity and hemostatic parameters. A set of single nucleotide polymorphisms (SNPs) in the vWF (rs216311, rs216321, rs1063856, rs1800378, rs1800383) and ADAMTS13 genes (rs2301612, rs28729234, rs34024143) were genotyped in 72 COVID-19 patients. Cross-sectional cohort analysis revealed no association of any polymorphism with disease severity. On the other hand, analysis of variance (ANOVA) uncovered associations with the following clinical parameters: (1) the rs216311 T allele with enhanced INR (international normalized ratio); (2) the rs1800383 C allele with elevated fibrinogen levels; and (3) the rs1063856 C allele with increased red blood cell count, hemoglobin, and creatinine levels. No association could be observed between the phenotypic data and the polymorphisms in the ADAMTS13 gene. Importantly, in silico protein conformational analysis predicted that these missense variants would display global conformational alterations, which might affect the stability and plasma levels of vWF. Our results imply that missense vWF variants might modulate the thrombotic risk in COVID-19. LA - English DB - MTMT ER - TY - JOUR AU - Papp, Alexandra Éva AU - Papp, Krisztián AU - Uzonyi, Barbara AU - Cserhalmi, Marcell AU - Csincsi, Ádám AU - Szabó, Zsóka AU - Bánlaki, Zsófia AU - Ermert, David AU - Prohászka, Zoltán AU - Erdei, Anna AU - Ferreira, Viviana P. AU - Blom, Anna M. AU - Józsi, Mihály TI - Complement Factor H-Related Proteins FHR1 and FHR5 Interact With Extracellular Matrix Ligands, Reduce Factor H Regulatory Activity and Enhance Complement Activation JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 13 PY - 2022 PG - 15 SN - 1664-3224 DO - 10.3389/fimmu.2022.845953 UR - https://m2.mtmt.hu/api/publication/32761919 ID - 32761919 N1 - MTA-ELTE Complement Research Group, Eötvös Loránd Research Network (ELKH), Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary MTA-ELTE Immunology Research Group, Eötvös Loránd Research Network (ELKH), Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary Department of Translational Medicine, Lund University, Malmo, Sweden Department of Internal Medicine and Haematology, Semmelweis University, Budapest, Hungary Research Group for Immunology and Haematology, Semmelweis University, Eötvös Loránd Research Network (Office for Supported Research Groups), Budapest, Hungary Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, OH, United States Cited By :1 Export Date: 2 December 2022 Correspondence Address: Józsi, M.; MTA-ELTE Complement Research Group, Hungary; email: mihaly.jozsi@ttk.elte.hu LA - English DB - MTMT ER - TY - JOUR AU - Molnár, Zsuzsanna AU - Rónai, Zsolt AU - Keszler, Gergely AU - Harsányi, László AU - Kontsek, Endre AU - Herold, Zoltán AU - Herold, Magdolna AU - Somogyi, Anikó AU - Bánlaki, Zsófia TI - Correlation between Expression Profiles of Key Signaling Genes in Colorectal Cancer Samples from Type 2 Diabetic and Non-Diabetic Patients JF - LIFE-BASEL J2 - LIFE-BASEL VL - 10 PY - 2020 IS - 9 PG - 13 SN - 2075-1729 DO - 10.3390/life10090216 UR - https://m2.mtmt.hu/api/publication/31607929 ID - 31607929 AB - Several lines of epidemiological and biochemical evidence support the association of type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC). T2DM has been shown to impinge on the transcriptome of colon tumor cells, promoting their proliferation and invasion. In order to gain insight into diabetes-specific modulation of colon cancer signaling, we analyzed gene expression patterns of more than five hundred genes encoding signaling proteins on TaqMan OpenArray panels from colonoscopic colorectal tumor samples of type 2 diabetic and non-diabetic patients. In total, 48 transcripts were found to be differentially expressed in tumors of T2DM patients as compared to healthy colon samples. Enrichment analysis with the g:GOSt (Gene Ontology Statistics) functional profiling tool revealed that the underlying genes can be classified into five signaling pathways (in decreasing order of significance: Wnt (wingless-type)/beta-catenin; Hippo; TNF (tumor necrosis factor); PI3K/Akt (phosphoinositide-3 kinase/protein kinase B), and platelet activation), implying that targeted downregulation of these signaling cascades might help combat CRC in diabetic patients. Transcript levels of some of the differentially expressed genes were also measured from surgically removed diabetic and non-diabetic CRC specimens by individual qPCR (quantitative real-time PCR) assays using the adjacent normal tissue mRNA levels as an internal control. The most significantly altered genes in diabetic tumor samples were largely different from those in non-diabetic ones, implying that T2DM profoundly alters the expression of signaling genes and presumably the biological characteristics of CRC. LA - English DB - MTMT ER - TY - JOUR AU - Molnár, Zsuzsanna AU - Bánlaki, Zsófia AU - Somogyi, Anikó AU - Herold, Zoltán AU - Herold, Magdolna AU - Guttman, András AU - Rónai, Zsolt AU - Keszler, Gergely TI - Diabetes-specific modulation of peripheral blood gene expression signatures in colorectal cancer JF - CURRENT MOLECULAR MEDICINE J2 - CURR MOL MED VL - 20 PY - 2020 IS - 10 SP - 773 EP - 780 PG - 8 SN - 1566-5240 DO - 10.2174/1566524020666200504084626 UR - https://m2.mtmt.hu/api/publication/31305664 ID - 31305664 LA - English DB - MTMT ER - TY - JOUR AU - Bánlaki, Zsófia TI - DNA Methylation, Speciation and Domestication JF - ADVANCED TECHNIQUES IN BIOLOGY & MEDICINE J2 - ADV TECHN BIOL MED VL - 5 PY - 2017 IS - 3 PG - 2 SN - 2379-1764 DO - 10.4172/2379-1764.1000234 UR - https://m2.mtmt.hu/api/publication/30686443 ID - 30686443 N1 - A közleményen szereplő DOI szám nem működik! LA - English DB - MTMT ER - TY - JOUR AU - Bánlaki, Zsófia AU - Cimarelli, G AU - Viranyi, Z AU - Kubinyi, Enikő AU - Sasvári-Székely, Mária AU - Rónai, Zsolt TI - DNA methylation patterns of behavior-related gene promoter regions dissect the gray wolf from domestic dog breeds JF - MOLECULAR GENETICS AND GENOMICS J2 - MOL GENET GENOMICS VL - 292 PY - 2017 IS - 3 SP - 685 EP - 697 PG - 13 SN - 1617-4615 DO - 10.1007/s00438-017-1305-5 UR - https://m2.mtmt.hu/api/publication/3238361 ID - 3238361 AB - A growing body of evidence highlights the relationship between epigenetics, especially DNA methylation, and population divergence as well as speciation. However, little is known about how general the phenomenon of epigenetics-wise separation of different populations is, or whether population assignment is, possible based on solely epigenetic marks. In the present study, we compared DNA methylation profiles between four different canine populations: three domestic dog breeds and their ancestor the gray wolf. Altogether, 79 CpG sites constituting the 65 so-called CpG units located in the promoter regions of genes affecting behavioral and temperamental traits (COMT, HTR1A, MAOA, OXTR, SLC6A4, TPH1, WFS1)-regions putatively targeted during domestication and breed selection. Methylation status of buccal cells was assessed using EpiTYPER technology. Significant inter-population methylation differences were found in 52.3% of all CpG units investigated. DNA methylation profile-based hierarchical cluster analysis indicated an unambiguous segregation of wolf from domestic dog. In addition, one of the three dog breeds (Golden Retriever) investigated also formed a separate, autonomous group. The findings support that population segregation is interrelated with shifts in DNA methylation patterns, at least in putative selection target regions, and also imply that epigenetic profiles could provide a sufficient basis for population assignment of individuals. LA - English DB - MTMT ER - TY - JOUR AU - Cimarelli, G AU - Viranyi, Z AU - Turcsán, Borbála AU - Rónai, Zsolt AU - Sasvári-Székely, Mária AU - Bánlaki, Zsófia TI - Social Behavior of Pet Dogs Is Associated with Peripheral OXTR Methylation JF - FRONTIERS IN PSYCHOLOGY J2 - FRONT PSYCHOL VL - 8 PY - 2017 PG - 15 SN - 1664-1078 DO - 10.3389/fpsyg.2017.00549 UR - https://m2.mtmt.hu/api/publication/3227977 ID - 3227977 N1 - Funding Agency and Grant Number: Austrian Science Fund (FWF) projectAustrian Science Fund (FWF) [I 1271-B24]; Hungarian Scientific Research FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA-ANN 107726] Funding text: This research was supported by the Austrian Science Fund (FWF) project I 1271-B24 and the Hungarian Scientific Research Fund project OTKA-ANN 107726. Furthermore, we are thankful to Royal Canin for supporting the Clever Dog Lab. AB - Oxytocin is a key modulator of emotional processing and social cognitive function. In line with this, polymorphisms of genes involved in oxytocin signaling, like the oxytocin receptor (OXTR) gene, are known to influence social behavior in various species. However, to date, no study has investigated environmental factors possibly influencing the epigenetic variation of the OXTR gene and its behavioral effects in dogs. Pet dogs form individualized and strong relationships with their owners who are central figures in the social environment of their dogs and therefore might influence the methylation levels of their OXTR gene. Here we set out to investigate whether DNA methylation within the OXTR promoter region of pet dogs is linked to their owner's interaction style and to the social behavior of the dogs. To be able to do so, we collected buccal epithelial cells and, in Study 1, we used pyrosequencing techniques to look for differentially methylated CpG sites in the canine OXTR promoter region on a heterogeneous sample of dogs and wolves of different ages and keeping conditions. Four identified sites (at positions -727, -751, -1371, and -1383 from transcription start site) showing more than 10% methylation variation were then, in Study 2, measured in triplicate in 217 pet Border Collies previously tested for reactions to an adverse social situation (i.e., approach by a threatening human) and with available data on their owners' interaction styles. We found that CpG methylation was significantly associated with the behavior of the dogs, in particular with the likelihood that dogs would hide behind their owner or remain passive when approached by a threatening human. On the other hand, CpG methylation was not related to the owners' behavior but to dog sex (at position -1371). Our findings underpin the complex relationship between epigenetics and behavior and highlight the importance of including epigenetic methods in the analysis of dog behavioral development. Further research is needed to investigate which environmental factors influence the epigenetic variation of the OXTR gene. LA - English DB - MTMT ER - TY - JOUR AU - Csincsi, Ádám AU - Weiszhar, Zsóka AU - Bánlaki, Zsófia AU - Uzonyi, Barbara AU - Cserhalmi, Marcell AU - Kárpáti, Éva AU - Tortajada, A AU - Caesar, JJE AU - Prohászka, Zoltán AU - Jokiranta, TS AU - Lea, SM AU - Rodríguez, de Córdoba S AU - Józsi, Mihály TI - FHR-1 binds to C-reactive protein and enhances rather than inhibits complement activation JF - JOURNAL OF IMMUNOLOGY J2 - J IMMUNOL VL - 199 PY - 2017 IS - 1 SP - 292 EP - 303 PG - 12 SN - 0022-1767 DO - 10.4049/jimmunol.1600483 UR - https://m2.mtmt.hu/api/publication/3221358 ID - 3221358 N1 - Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Lendület Complement Research Group, Department of Immunology, ELTE Eötvös Loránd University, Pazmany Peter setany 1/c, Budapest, H-1117, Hungary Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Immunology Research Group, Department of Immunology, ELTE Eötvös Loránd University, Budapest, 1117, Hungary Departamento Medicina Celular y Molecular, Centro de Investigaciones Biológicas, Madrid, 28040, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, 28040, Spain Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, United Kingdom Research Laboratory, 3rd Department of Internal Medicine, Semmelweis University, Budapest, H-1125, Hungary Research Programs Unit, Immunobiology, Haartman Institute, University of Helsinki, Helsinki, FI-00014, Finland Cited By :5 Export Date: 19 December 2018 CODEN: JOIMA Correspondence Address: Józsi, M.; Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Lendület Complement Research Group, Department of Immunology, ELTE Eötvös Loránd University, Pazmany Peter setany 1/c, Hungary; email: mihaly.jozsi@gmx.net Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Lendület Complement Research Group, Department of Immunology, ELTE Eötvös Loránd University, Pazmany Peter setany 1/c, Budapest, H-1117, Hungary Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Immunology Research Group, Department of Immunology, ELTE Eötvös Loránd University, Budapest, 1117, Hungary Departamento Medicina Celular y Molecular, Centro de Investigaciones Biológicas, Madrid, 28040, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, 28040, Spain Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, United Kingdom Research Laboratory, 3rd Department of Internal Medicine, Semmelweis University, Budapest, H-1125, Hungary Research Programs Unit, Immunobiology, Haartman Institute, University of Helsinki, Helsinki, FI-00014, Finland Cited By :7 Export Date: 2 August 2019 CODEN: JOIMA Correspondence Address: Józsi, M.; Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Lendület Complement Research Group, Department of Immunology, ELTE Eötvös Loránd University, Pazmany Peter setany 1/c, Hungary; email: mihaly.jozsi@gmx.net Chemicals/CAS: C reactive protein, 9007-41-4; complement component C1q, 80295-33-6; complement component C3, 80295-41-6; complement factor H, 80295-65-4; classical complement pathway C3 C5 convertase, 56626-15-4; complement factor I, 80295-66-5; C-Reactive Protein; CFHR1 protein, human; Complement C3-C5 Convertases; Complement C3b; Complement C3b Inactivator Proteins; Complement Factor H; complement factor H, human; Ligands; PTX3 protein; Serum Amyloid P-Component Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Lendület Complement Research Group, Department of Immunology, ELTE Eötvös Loránd University, Pazmany Peter setany 1/c, Budapest, H-1117, Hungary Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Immunology Research Group, Department of Immunology, ELTE Eötvös Loránd University, Budapest, 1117, Hungary Departamento Medicina Celular y Molecular, Centro de Investigaciones Biológicas, Madrid, 28040, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, 28040, Spain Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, United Kingdom Research Laboratory, 3rd Department of Internal Medicine, Semmelweis University, Budapest, H-1125, Hungary Research Programs Unit, Immunobiology, Haartman Institute, University of Helsinki, Helsinki, FI-00014, Finland Cited By :9 Export Date: 14 October 2019 CODEN: JOIMA Correspondence Address: Józsi, M.; Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Lendület Complement Research Group, Department of Immunology, ELTE Eötvös Loránd University, Pazmany Peter setany 1/c, Hungary; email: mihaly.jozsi@gmx.net Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Lendület Complement Research Group, Department of Immunology, ELTE Eötvös Loránd University, Pazmany Peter setany 1/c, Budapest, H-1117, Hungary Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Immunology Research Group, Department of Immunology, ELTE Eötvös Loránd University, Budapest, 1117, Hungary Departamento Medicina Celular y Molecular, Centro de Investigaciones Biológicas, Madrid, 28040, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, 28040, Spain Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, United Kingdom Research Laboratory, 3rd Department of Internal Medicine, Semmelweis University, Budapest, H-1125, Hungary Research Programs Unit, Immunobiology, Haartman Institute, University of Helsinki, Helsinki, FI-00014, Finland Cited By :9 Export Date: 16 October 2019 CODEN: JOIMA Correspondence Address: Józsi, M.; Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Lendület Complement Research Group, Department of Immunology, ELTE Eötvös Loránd University, Pazmany Peter setany 1/c, Hungary; email: mihaly.jozsi@gmx.net Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Lendület Complement Research Group, Department of Immunology, ELTE Eötvös Loránd University, Pazmany Peter setany 1/c, Budapest, H-1117, Hungary Hungarian Academy of Sciences-Eötvös Loránd University, MTA-ELTE Immunology Research Group, Department of Immunology, ELTE Eötvös Loránd University, Budapest, 1117, Hungary Departamento Medicina Celular y Molecular, Centro de Investigaciones Biológicas, Madrid, 28040, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, 28040, Spain Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, United Kingdom Research Laboratory, 3rd Department of Internal Medicine, Semmelweis University, Budapest, H-1125, Hungary Research Programs Unit, Immunobiology, Haartman Institute, University of Helsinki, Helsinki, FI-00014, Finland Cited By :16 Export Date: 28 July 2021 CODEN: JOIMA Correspondence Address: Józsi, M.; Hungarian Academy of Sciences-Eötvös Loránd University, Pazmany Peter setany 1/c, Hungary; email: mihaly.jozsi@gmx.net AB - Factor H-related protein (FHR) 1 is one of the five human FHRs that share sequence and structural homology with the alternative pathway complement inhibitor FH. Genetic studies on disease associations and functional analyses indicate that FHR-1 enhances complement activation by competitive inhibition of FH binding to some surfaces and immune proteins. We have recently shown that FHR-1 binds to pentraxin 3. In this study, our aim was to investigate whether FHR-1 binds to another pentraxin, C-reactive protein (CRP), analyze the functional relevance of this interaction, and study the role of FHR-1 in complement activation and regulation. FHR-1 did not bind to native, pentameric CRP, but it bound strongly to monomeric CRP via its C-terminal domains. FHR-1 at high concentration competed with FH for CRP binding, indicating possible complement deregulation also on this ligand. FHR-1 did not inhibit regulation of solid-phase C3 convertase by FH and did not inhibit terminal complement complex formation induced by zymosan. On the contrary, by binding C3b, FHR-1 allowed C3 convertase formation and thereby enhanced complement activation. FHR-1/CRP interactions increased complement activation via the classical and alternative pathways on surfaces such as the extracellular matrix and necrotic cells. Altogether, these results identify CRP as a ligand for FHR-1 and suggest that FHR-1 enhances, rather than inhibits, complement activation, which may explain the protective effect of FHR-1 deficiency in age-related macular degeneration. LA - English DB - MTMT ER -