Beáta Szebeni

Semmelweis University, Budapeŝto, Budapest, Hungary

Are you Beáta Szebeni?

Claim your profile

Publications (37)72.5 Total impact


  • No preview · Article · Sep 2014 · Pediatric Nephrology

  • No preview · Conference Paper · May 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction and Aims: In our previous studies we found that exercise partially prevents chronic kidney disease (CKD)-induced muscle atrophy. Effective therapeutic strategies to treat Chronic Kidney Disease (CKD)-induced muscle atrophy are urgently needed. Low frequency electrical stimulation (LFES) induces muscle contraction which mimics acupuncture and exercise, and may be effective in preventing muscle atrophy. Methods: CKD was induced in 20-25g mice by 5/6th nephrectomy. CKD and control mice were treated with LFES for 15 days. Results: LFES prevented soleus and EDL muscle weight loss in CKD mice (p<0.05, LFES/CKD vs. CKD) as well as loss of hind-limb muscle grip. LFES countered the CKD-induced decline in the IGF-1 signaling pathway, leading to increased protein synthesis, decreased protein degradation and increased myogenesis markers. There is an acute (immediate) response phase during which inflammation cytokines (IFN and IL-6) increased. M1 macrophage markers (pro-inflammation: IL-1β) were also increased acutely, but M2 markers (anti-inflammation: arg-1, IL-10 and IL-4) were increased 2-days after initiation of LFES. In addition, microRNA-1 and -206 were decreased in the acute phase after starting LFES. Conclusions: We conclude that LFES ameliorates CKD-induced skeletal muscle atrophy by up-regulation of the IGF-1 signaling pathway which improves protein metabolism and promotes myogenesis. The potential mechanisms leading to upregulation of IGF are 1) decrease of microRNA-1 and -206 in the early phase of LEFS resulting in reversal of the inhibition of IGF-1 production by these microRNAs or 2) direct secretion of IGF-1 by M2 macrophages in the later phase inflammatory response.
    Full-text · Article · May 2014 · Nephrology Dialysis Transplantation
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recently, it has been suggested that the gene called Parkinson's disease 7 (PARK7) might be an upstream activator of hypoxia-inducible factor (HIF)-1α, which plays a major role in sustaining intestinal barrier integrity. Furthermore, PARK7 has been proposed to participate in the Toll-like receptor (TLR)-dependent regulation of the innate immune system. Our aim was to investigate the involvement of PARK7 in the pathogenesis of coeliac disease (CD). Duodenal biopsy specimens were collected from 19 children with untreated CD, five children with treated CD (maintained on gluten-free diet), and ten children with histologically normal duodenal biopsies. PARK7 mRNA expression and protein level were determined by real-time polymerase chain reaction (PCR) and Western blot, respectively. Localization of PARK7 was visualized by immunofluorescence staining. Protein level of PARK7 increased in the duodenal mucosa of children with untreated CD compared to children with treated CD or to control biopsies (p <0.03). We detected intensive PARK7 staining in the epithelial cells and lamina propria of the duodenal mucosa of children with untreated CD compared with that in control biopsies. Our finding that mucosal expression of PARK7 is increased suggests that PARK7 is involved in the pathogenesis of gastrointestinal diseases, notably CD. Our results suggest that PARK7 may alter processes mediated by HIF-1α and TLR4, which supports a role for PARK7 in the maintenance of epithelial barrier integrity, immune homeostasis, or apoptosis.
    Full-text · Article · Jul 2013 · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
  • [Show abstract] [Hide abstract]
    ABSTRACT: Coeliac disease is a genetically predisposed complex inflammatory gastrointestinal disease which is characterized by a chronic stress reaction induced by wheat, rye and barley gluten. The aim of our review article is to summarize the role of heat shock proteins (HSP) in the pathomechanism of coeliac disease. HSPs are higly conservated molecular chaperones with different molecule masses. They are present in all organism referring to the universality of the heat shock response. In the duodenal mucosa of patients with coeliac disease the expression of HSPs is increased which maycontribute to the development of the disorder.
    No preview · Article · Jan 2013 · Orvosképzés
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate intestinal alkaline phosphatase (iAP) in the intestinal mucosa of children with inflammatory bowel disease (IBD). Colonic biopsy samples were taken from 15 newly diagnosed IBD patients and from 10 healthy controls. In IBD patients, specimens were obtained both from inflamed and non-inflamed areas. The iAP mRNA and protein expression was determined by reverse transcription-polymerase chain reaction and Western blotting analysis, respectively. Tissue localization of iAP and Toll-like receptor (TLR) 4 was investigated by immunofluorescent staining. The iAP protein level in the inflamed mucosa of children with Crohn's disease (CD) and ulcerative colitis (UC) was significantly decreased when compared with controls (both P < 0.05). Similarly, we found a significantly decreased level of iAP protein in the inflamed mucosa in CD compared with non-inflamed mucosa in CD (P < 0.05). In addition, the iAP protein level in inflamed colonic mucosa in patients with UC was decreased compared with non-inflamed mucosa in patients with CD (P < 0.05). iAP protein levels in the non-inflamed mucosa of patients with CD were similar to controls. iAP mRNA expression in inflamed colonic mucosa of children with CD and UC was not significantly different from that in non-inflamed colonic mucosa with CD. Expression of iAP mRNA in patients with non-inflamed mucosa and in controls were similar. Co-localization of iAP with TLR4 showed intense staining with a dotted-like pattern. iAP was present in the inflamed and non-inflamed mucosa of patients with CD, UC, and in control biopsy specimens, irrespective of whether it was present in the terminal ileum or in the colon. However, the fluorescent signal of TLR4 was more pronounced in the colon compared with the terminal ileum in all groups studied. Lower than normal iAP protein levels in inflamed mucosa of IBD patients may indicate a role for iAP in inflammatory lesions in IBD. Based on our results, administration of exogenous iAP enzyme to patients with the active form of IBD may be a therapeutic option.
    Full-text · Article · Jul 2012 · World Journal of Gastroenterology
  • [Show abstract] [Hide abstract]
    ABSTRACT: INTRODUCTION AND AIMS: Ultimate objective of nanoparticles-based therapy is to functionalize them in micro-disease environment without any side effects. Here, we revealed that our nitroxide radical-containing nanoparticles (TEMPONano) disintegrate within renal acidic area by ischemia and act as a scavenger of reactive oxygen species (ROS) to recover from damage. METHODS: TEMPONano was prepared by self assembly of amphiphilic block copolymer possessing nitroxide radicals, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) via amine linkage as a side chain of the hydrophobic segment. The nanoparticle disintegrated at pH below 7.0 due to the protonation of the amino groups in the hydrophobic core, resulting in improvement of ROS scavenging activity. Using renal ischemia-reperfusion model in mice, the therapeutic effect of TEMPONano on ROS damage was evaluated. RESULTS: Contrary to the nitroxide radical-containing nanoparticle without pH-triggered disintegration, the pH-sensitive TEMPONano showed extremely higher ROS scavenging activity and therapeutic effect. The disintegration of pH-sensitive TEMPONano in injured kidney area was confirmed by electron spin resonance spectra, which is first evidence of real therapeutic effect of the environmental-sensitive specific disintegration of nanoparticle worked in vivo. The attenuation of functional and histological indices of injury resulted from the ability of TEMPONano to reduce oxidation of lipid and generation of pro-inflammatory cytokine. Further studies showed the TEMPONano disintegrated in kidney area, although it forms polymeric micelle in blood, which was confirmed by EPR spectra. Moreover, TEMPNano completely prevented the decrease in blood pressure, which is side effect of low-molecular-weight TEMPO derivatives. CONCLUSIONS: In conclusion, pH-sensitive TEMPONano effectively reduced the renal dysfunction and injury caused by renal ischemia-reperfusion, compared with non-pH-sensitive nanoparticle and low-molecular-weight TEMPO compounds, which was due to the disintegration of TEMPONano under the renal acidic area. View larger version: In this window In a new window Download as PowerPoint Slide
    No preview · Article · Jun 2011 · CKJ: Clinical Kidney Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Several studies reported sexual dimorphism in the signaling mechanisms of renal ischemia/reperfusion (I/R). The anti-apoptotic serum and glucocorticoid-regulated kinase-1 (SGK-1) is up-regulated and has a significant protective role in renal I/R. SGK-1 has several target molecules, and inhibition of the inducible nitric oxide synthase (iNOS) transcription is one of its effector mechanisms. The objective of the present study was to examine if there is a gender-specific expression and activation of SGK-1 during renal I/R injury. In vitro, treatment of HK-2 kidney proximal tubular cells with different concentrations of 17-beta estradiol had no effect, whereas testosterone increased SGK-1 abundance in a dose-dependent manner. In vivo, in a rat model of unilateral renal I/R injury, there was a higher SGK-1 expression and phosphorylation in males 2 and 24 h after ischemia paralleled by reduction in the mRNA expression of iNOS compared to females. Deprivation of testosterone by castration of males resulted in decreased SGK-1 protein level at all time-points and reduced phosphorylation 2 and 24 h after reperfusion. Our results suggest that testosterone up-regulates SGK-1 in the kidney contributing to sexual dimorphisms in the cell signalling machinery. The significance of the testosterone-regulated SGK-1 level and activity in the kidney needs further investigations.
    Full-text · Article · Jun 2011 · Cellular Physiology and Biochemistry
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Heat shock protein (HSP) 72, a known chaperone, has potential epithelial barrier protecting, antiapoptotic, and immune system regulatory effects; therefore, our aim was to study its involvement in the pathology of celiac disease (CD). Duodenal biopsy specimens were collected from children with untreated and treated CD and from controls. mRNA expression, protein level, and localization of HSP72 were determined. Elevated HSP72 mRNA expression and higher protein levels were found in the duodenal mucosa of children with untreated CD as well as in children with treated CD compared with those in controls. In the duodenal mucosa of children with treated CD, HSP72 mRNA expression was decreased and HSP72 protein levels were lower than those in children with untreated CD. We detected intensive HSP72 staining in the villous enterocytes and immune cells of the lamina propria in the duodenal villi of children with untreated CD compared with that in controls. The increased expression and altered localization of HSP72 in CD indicate that HSP72 should have a role in protection against gliadin-induced cytotoxicity. HSP72 may exert antiapoptotic effect and contribute to preservation of intestinal epithelial barrier integrity. Moreover, HSP72 as a ligand of TLR2 and TLR4 may promote innate immune responses and warn the cells of the potential injury.
    Full-text · Article · Nov 2010 · Journal of pediatric gastroenterology and nutrition
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of our study was to investigate the prevalence of CD4 T lymphocyte subsets and their commitment to TH1 or TH2 direction in 10 infants with allergic colitis (AC) and 10 healthy controls. Infants with AC presented with a higher ratio of naïve to memory cells, lower prevalence of activated CD4CD25 cells and FoxP3 regulatory cells, and a shift to TH2 direction in balance compared with controls. These alterations are normalized upon cessation of AC symptoms on elemental L-amino acid formula. These findings suggest the importance of antigen exposure in AC in infancy.
    No preview · Article · Nov 2010 · Journal of pediatric gastroenterology and nutrition
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Histamine and vascular endothelial growth factor (VEGF) have been implicated in the pathogenesis of allergic asthma; they enhance inflammation, vascular permeability, and mucus secretion. Histamine was suggested to alter the level of VEGF via the H2 receptors. Here the authors have applied histidine decarboxylase gene-targeted (HDC(-/-)) mice, lacking histamine, to investigate the effect of histamine deficiency on VEGF expression in an animal model of asthma. HDC(-/-) and wild-type (WT) mice were sensitized and challenged with ovalbumin (OVA). VEGF mRNA expression and protein level were determined in the lung. Number of VEGF-positive immune cells of bronchoalveolar lavage (BAL) and their intracellular VEGF content were measured by flow cytometry. VEGF protein level in the lung and in the BAL cells was increased in OVA treated (HDC(-/-)(ova) as well as in WT(ova)) animals compared to their controls. However, there was no difference in the VEGF levels between HDC(-/-) or WT animals, either in the lung or in the BAL cells. In conclusion, increased VEGF production of the lung or BAL immune cells can be induced by allergen provocation independently from the genetic background of the animals. These data suggest that VEGF-mediated allergic processes can persist in the absence of histamine.
    Full-text · Article · Sep 2010 · Experimental Lung Research
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Anatomical malformations of the kidney and urinary tract account for 17% of pediatric renal transplantation procedures. Heat shock proteins (HSPs) are molecular chaperones with a protective function that promotes cell survival. HSP72 is an endogenous ligand for toll-like receptor TLR4, thereby stimulating innate immunity. Both in adults and children, decreased expression of HSP70s is associated with a number of kidney diseases. To assess the prevalence of HSPA1A G(190)C, HSPA1B A(1267)G, and TLR4 A(896)G polymorphisms in children who had undergone kidney transplantation. Genotypes were analyzed using allele-specific polymerase chain reaction in 41 pediatric recipients. Allelic prevalence was related to reference values in 65 age- and sex-matched healthy children. Clinical data did not reveal a difference between any of the groups. HSPA1B (1267)GG genotype and HSPA1B (1267)G allele were observed more frequently in the transplant recipients compared with the control group: AA vs AG: odds ratio [OR], 12.6; 95% confidence interval [CI], 1.58-100.0; P = .004; AA vs GG: OR, 20.80; 95% CI, 2.32-187.00; P = .01; and A vs G: OR, 2.10; 95% CI, 1.19-3.07; P = .01. Furthermore, the prevalence of the HSPA1B (1267)GG genotype was greater in transplant recipients with vs without urinary tract malformations: AG vs GG: OR, 0.10; 95% CI, 0.09-0.48; P = .007. No differences were observed in the other studied polymorphisms. Our findings suggest an association between the carrier status of HSPA1B (1267)G with urinary tract malformations, leading to end-stage renal disease requiring kidney transplantation. This observation raises further questions about the clinical and therapeutic relevance of this polymorphism to pediatric nephrology.
    Full-text · Article · Jul 2010 · Transplantation Proceedings
  • [Show abstract] [Hide abstract]
    ABSTRACT: Th17 cells are the newly described subset of the CD4(+) T lymphocytes. Activated Th17 cells are characterized by their ability to produce IL-17A and other pro-inflammatory cytokines. IL-17A regulates immune function through its cell-surface receptor expressed on epithelial-and endothelial cells, fibroblasts and leukocytes by promoting neutrophil recruitment and releasing further pro-inflammatory mediators. Failures of the susceptible balance of the immunoregulation may lead to unchecked immune response and autoimmune diseases. The central role of Th17 cells and cytokines produced by Th17 cells were confirmed in a wide variety of human autoimmune diseases, including rheumatoid arthritis. Recently Th17 cells and its cytokines come into the focus of immunological research as potential therapeutic targets.
    No preview · Article · Jun 2010 · Orvosi Hetilap
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previously, it has been suggested that hypoxia-inducible factor (HIF) 1 signaling may play determinative role in the maintenance of the barrier function of the intestinal epithelium in inflammatory bowel disease. Our aim was to depict the alteration of HIF-1alpha and related genes in celiac disease (CD) where the importance of the barrier function is well known. Duodenal biopsy specimens were collected from 16 children with untreated CD, 9 children with treated CD and 10 controls. HIF-1alpha, trefoil factor 1 (TFF1), ecto-5-prime nucleotidase (CD73), and multi drug resistance gene 1 (MDR1) mRNA and HIF-1alpha protein expression were determined by real-time PCR and Western blot, respectively. Localization of HIF-1alpha was determined by immunofluorescent staining. We found increased HIF-1alpha and TFF1 mRNA and HIF-1alpha protein expression in the duodenal mucosa of children with untreated CD compared with controls or children with treated CD (p < 0.05). In untreated CD children, HIF-1alpha staining was present in cytoplasmic and nuclear region of the villous enterocytes. In treated CD mRNA expression of CD73 and MDR1 were increased compared with controls (p < 0.01 and 0.05, respectively). Our results of increased mucosal HIF-1alpha expression in CD children suggest the contribution of this signaling pathway in the pathomechanism of CD.
    Full-text · Article · May 2010 · Pediatric Research
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: Enterocyte apoptosis induced by activated intraepithelial lymphocytes is increased in coeliac disease (CD). Serum- and glucocorticoid-regulated kinase-1 (SGK1) is a serine/threonine protein kinase that may inhibit apoptosis and compensate for the excessive death of surface epithelial cells. The significance of SGK1 in CD is elusive so far. The aim of this study was to characterise the expression and localisation of SGK1 in duodenal biopsy samples taken from children with untreated CD, children with treated CD, and controls. Patients and Methods: Duodenal biopsy specimens were collected from 16 children with untreated CD, 9 children with treated CD, and 10 controls. The mRNA expression of SGK1 was determined by real-time reverse transcription-polymerase chain reaction. SGK1 and phosphorylated (P)-SGK1 protein levels and their localisation were determined by Western blot and immunfluorescent staining, respectively. Results: We found increased SGK1-mRNA expression as well as higher SGK1 and P-SGK1 protein levels in the duodenal mucosa of children with untreated CD compared with controls. In the duodenal mucosa of children with treated CD, SGK1-mRNA expression was decreased and SGK1 and P-SGK1 protein levels were lower than in untreated CD. SGK1 and P-SGK1 staining intensity was stronger in duodenal villous enterocytes of children with untreated CD compared with treated CD. Conclusions: Our results of increased expression of SGK1 in untreated CD may suggest its contribution to the enterocyte survival in this disease.
    Full-text · Article · Jan 2010 · Journal of Pediatric Gastroenterology and Nutrition
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Erythropoietin (EPO) protects the kidneys from ischemia/reperfusion (I/R) injury; however, the exact signalling mechanisms are not fully understood. The serum and glucocorticoid-regulated kinase 1 (SGK1) is an anti-apoptotic protein kinase regulated through the phosphatidylinositol 3-kinase (PI3-kinase) pathway by cellular stimuli, hormones and growth factors. The objective of the present study was to examine the role of SGK1 in the renoprotective effects of EPO in renal I/R injury. In vitro, cultures of HEK293 cells were exposed to 16h hypoxia. Incubation with EPO at a doses of 400U/ml exerted a protective effect on cell death assessed by LDH release and Annexin V FACS analysis. This was paralleled by up-regulation of SGK1 expression, as well as phosphorylation. Downregulation of SGK1 expression by small interfering RNA technique ameliorated the anti-apoptotic effect of EPO treatment. In an in vivo rat model of unilateral renal I/R injury, rats were treated with 500U/kg EPO 24h prior to ischemia. EPO resulted in less severe tissue injury and ameliorated the elevation in creatinine and urea nitrogen levels 24h after reperfusion. Furthermore, SGK1 expression and phosphorylation were higher in EPO compared to vehicle-treated rats as demonstrated by real-time PCR, Western blot and immunofluorescence technique. We conclude that EPO protects from renal I/R injury and SGK1 might contribute to the mediation of EPO effects under ischemic conditions.
    Full-text · Article · Dec 2009 · Biochemical pharmacology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Galectin-9 (Gal-9) is a member of the growing family of beta-galactoside-binding lectins. Gal-9 is an eosinophil chemoattractant and inducer of Th1 cell apoptosis. These effects suggest its potential role in the pathogenesis of asthma. Our aim was to study the expression of Gal-9 in an ovalbumin (OVA)-induced mouse model of allergic asthma. To investigate the significance of Gal-9 in allergic inflammation and airway hyperresponsiveness (AHR), a group of BALB/c mice was sensitized and challenged with OVA (G(OVA)). Another group of animals was allergized with OVA and also treated with dexamethasone (DEX) (G(OVA+DEX)). The control group (G(PBS)) received phosphate-buffered saline instead of OVA as placebo. Airway reactivity to intravenous methacholine was assessed. The percentage of Gal-9-positive cells and their intracellular Gal-9 content and Th1/Th2 cytokine levels in the bronchoalveolar lavage (BAL) were determined by flow cytometry. Gal-9 mRNA expression and protein level were measured in the lung tissue by real-time RT-PCR and Western blot. In G(OVA )mice, airway inflammation and mucus hypersecretion developed. DEX treatment inhibited the main features of experimental asthma. The number of Gal-9-positive lymphocytes, eosinophil and neutrophil granulocytes and the levels of Th2 cytokines were higher in the BAL of G(OVA) compared to G(PBS) or G(OVA+DEX )mice. Moreover, Gal-9 protein level was elevated in the lungs of G(OVA) mice. These results suggest that Gal-9 plays a role as a mediator contributing to the development of allergic airway inflammation. Gal-9 may serve as a recruiter of eosinophil granulocytes and promoter of Th2 dominance.
    Full-text · Article · Oct 2009 · International Archives of Allergy and Immunology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Angiogenic factors such as vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) contribute to development of retinopathy of prematurity (ROP). We aimed to test whether polymorphisms of these factors are associated with ROP. VEGF(-2578) and Ang2(-35) polymorphisms were analyzed with PCR-RFLP method in 200 preterm infants without ROP or with ROP stages 1-5. Our results suggest that there is no association between carrier state of VEGF(-2578) and Ang2(-35) and risk of ROP in preterm infants. The prevalence of VEGF(-2578) "A" allele was lower in preterm boys with severe ROP (stages 4-5) than in those without or with mild ROP (stages 1-3).
    No preview · Article · Jul 2009 · Current Eye Research

  • No preview · Article · May 2009 · Lung Cancer
  • Aron Cseh · Beáta Szebeni · Balázs Szalay · Barna Vásárhelyi
    [Show abstract] [Hide abstract]
    ABSTRACT: Alteration of apoptotic processes plays a central role in the development and progression of several chronic disorders. Proteins responsible for the regulation of apoptosis are therapeutic targets; these include the Akt enzyme. Akt enzyme is expressed in most cell types. Akt activation is regulated by growth factors, insulin, and also environmental factors as altered oxygen tension and high temperature. Akt is a central regulator of cellular metabolism and survival. Akt function is reportedly altered in some disorders. An increased activity of Akt has been described in prostate, breast, colon, and pancreatic cancer, as well as in hematological malignancies. Akt is also a factor in the pathomechanism of diabetes as it determines beta-cell apoptosis of Langerhans islets and insulin sensitivity of the cells. Several studies revealed that some of the marketed drugs including statins, thiazolidinediones and ACE inhibitors modulate Akt activity. There are efforts to develop specific Akt inhibitors that may improve the efficacy of chemotherapy. Triciribine and perifosine are two Akt inhibitors in developmental phase 1 and 2 that may improve survival in breast cancer, pancreas cancer, gastrointestinal stroma tumor, sarcoma and melanoma, and in hematological malignancy.
    No preview · Article · Mar 2009 · Orvosi Hetilap