TY - JOUR A1 - Schneider, Andreas A1 - Schneider, Markus P. A1 - Scharnagl, Hubert A1 - Jardine, Alan G. A1 - Wanner, Christoph A1 - Drechsler, Christiane T1 - Predicting erythropoietin resistance in hemodialysis patients with type 2 diabetes JF - BMC Nephrology N2 - Background: Resistance to ESAs (erythropoietin stimulating agents) is highly prevalent in hemodialysis patients with diabetes and associated with an increased mortality. The aim of this study was to identify predictors for ESA resistance and to develop a prediction model for the risk stratification in these patients. Methods: A post-hoc analysis was conducted of the 4D study, including 1015 patients with type 2 diabetes undergoing hemodialysis. Determinants of ESA resistance were identified by univariate logistic regression analyses. Subsequently, multivariate models were performed with stepwise inclusion of significant predictors from clinical parameters, routine laboratory and specific biomarkers. Results: In the model restricted to clinical parameters, male sex, shorter dialysis vintage, lower BMI, history of CHF, use of ACE-inhibitors and a higher heart rate were identified as independent predictors of ESA resistance. In regard to routine laboratory markers, lower albumin, lower iron saturation, higher creatinine and higher potassium levels were independently associated with ESA resistance. With respect to specific biomarkers, higher ADMA and CRP levels as well as lower Osteocalcin levels were predictors of ESA resistance. Conclusions: Easily obtainable clinical parameters and routine laboratory parameters can predict ESA resistance in diabetic hemodialysis patients with good discrimination. Specific biomarkers did not meaningfully further improve the risk prediction of ESA resistance. Routinely assessed data can be used in clinical practice to stratify patients according to the risk of ESA resistance, which may help to assign appropriate treatment strategies. KW - type 2 diabetes KW - heodialysis patients Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128695 VL - 14 IS - 67 ER - TY - JOUR A1 - Schneider, Andreas A1 - Schneider, Markus P. A1 - Krieter, Detlef H. A1 - Genser, Bernd A1 - Scharnagl, Hubert A1 - Stojakovic, Tatjana A1 - Wanner, Christoph A1 - Drechsler, Christiane T1 - Effect of high-flux dialysis on circulating FGF-23 levels in end-stage renal disease patients: results from a randomized trial JF - PLoS ONE N2 - Background In patients undergoing maintenance hemodialysis (HD), increased levels of circulating fibroblast growth factor-23 (FGF-23) are independently associated with cardiovascular events and mortality. Interventional strategies aiming to reduce levels of FGF-23 in HD patients are of particular interest. The purpose of the current study was to compare the impact of high-flux versus low-flux HD on circulating FGF-23 levels. Methods We conducted a post-hoc analysis of the MINOXIS study, including 127 dialysis patients randomized to low-flux (n = 62) and high-flux (n = 65) HD for 52 weeks. Patients with valid measures for FGF-23 investigated baseline and after 52 weeks were included. Results Compared to baseline, a significant increase in FGF-23 levels after one year of low-flux HD was observed (Delta plasma FGF-23: +4026 RU/ml; p < 0.001). In contrast, FGF-23 levels remained stable in the high flux group (Delta plasma FGF-23: +373 RU/ml, p = 0.70). The adjusted difference of the absolute change in FGF-23 levels between the two treatment groups was statistically significant (p < 0.01). Conclusions Over a period of 12 months, high-flux HD was associated with stable FGF-23 levels, whereas the low-flux HD group showed an increase of FGF-23. However, the implications of the different FGF 23 time-trends in patients on high flux dialysis, as compared to the control group, remain to be explored in specifically designed clinical trials. KW - chronic kidney disease KW - left ventricular hypertrophy KW - phosphate homeostasis KW - hemodialysis KW - mortality KW - fibroblast growth factor-23 KW - mineral metabolism KW - parathyroid hormone KW - cardiovascular events Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148559 VL - 10 IS - 5 ER - TY - JOUR A1 - Marenholz, Ingo A1 - Esparza-Gordillo, Jorge A1 - Rüschendorf, Franz A1 - Bauerfeind, Anja A1 - Strachan, David P. A1 - Spycher, Ben D. A1 - Baurecht, Hansjörg A1 - Magaritte-Jeannin, Patricia A1 - Sääf, Annika A1 - Kerkhof, Marjan A1 - Ege, Markus A1 - Baltic, Svetlana A1 - Matheson, Melanie C. A1 - Li, Jin A1 - Michel, Sven A1 - Ang, Wei Q. A1 - McArdle, Wendy A1 - Arnold, Andreas A1 - Homuth, Georg A1 - Demenais, Florence A1 - Bouzigon, Emmanuelle A1 - Söderhäll, Cilla A1 - Pershagen, Göran A1 - de Jongste, Johan C. A1 - Postma, Dirkje S. A1 - Braun-Fahrländer, Charlotte A1 - Horak, Elisabeth A1 - Ogorodova, Ludmila M. A1 - Puzyrev, Valery P. A1 - Bragina, Elena Yu A1 - Hudson, Thomas J. A1 - Morin, Charles A1 - Duffy, David L. A1 - Marks, Guy B. A1 - Robertson, Colin F. A1 - Montgomery, Grant W. A1 - Musk, Bill A1 - Thompson, Philip J. A1 - Martin, Nicholas G. A1 - James, Alan A1 - Sleiman, Patrick A1 - Toskala, Elina A1 - Rodriguez, Elke A1 - Fölster-Holst, Regina A1 - Franke, Andre A1 - Lieb, Wolfgang A1 - Gieger, Christian A1 - Heinzmann, Andrea A1 - Rietschel, Ernst A1 - Keil, Thomas A1 - Cichon, Sven A1 - Nöthen, Markus M. A1 - Pennel, Craig E. A1 - Sly, Peter D. A1 - Schmidt, Carsten O. A1 - Matanovic, Anja A1 - Schneider, Valentin A1 - Heinig, Matthias A1 - Hübner, Norbert A1 - Holt, Patrick G. A1 - Lau, Susanne A1 - Kabesch, Michael A1 - Weidinger, Stefan A1 - Hakonarson, Hakon A1 - Ferreira, Manuel A. R. A1 - Laprise, Catherine A1 - Freidin, Maxim B. A1 - Genuneit, Jon A1 - Koppelman, Gerard H. A1 - Melén, Erik A1 - Dizier, Marie-Hélène A1 - Henderson, A. John A1 - Lee, Young Ae T1 - Meta-analysis identifies seven susceptibility loci involved in the atopic march JF - Nature Communications N2 - Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P = 2.1 x 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P = 5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema. KW - chromosome 11Q13 KW - risk KW - genomewide association KW - hay fever KW - birth cohort KW - filaggrin mutations KW - food allergy KW - juvenile myoclonic epilepsy KW - childhood asthma KW - dermatitis Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139835 VL - 6 IS - 8804 ER - TY - JOUR A1 - Schneider, Johannes A1 - Klein, Teresa A1 - Mielich-Süss, Benjamin A1 - Koch, Gudrun A1 - Franke, Christian A1 - Kuipers, Oskar P. A1 - Kovács, Ákos T. A1 - Sauer, Markus A1 - Lopez, Daniel T1 - Spatio-temporal Remodeling of Functional Membrane Microdomains Organizes the Signaling Networks of a Bacterium JF - PLoS Genetics N2 - Lipid rafts are membrane microdomains specialized in the regulation of numerous cellular processes related to membrane organization, as diverse as signal transduction, protein sorting, membrane trafficking or pathogen invasion. It has been proposed that this functional diversity would require a heterogeneous population of raft domains with varying compositions. However, a mechanism for such diversification is not known. We recently discovered that bacterial membranes organize their signal transduction pathways in functional membrane microdomains (FMMs) that are structurally and functionally similar to the eukaryotic lipid rafts. In this report, we took advantage of the tractability of the prokaryotic model Bacillus subtilis to provide evidence for the coexistence of two distinct families of FMMs in bacterial membranes, displaying a distinctive distribution of proteins specialized in different biological processes. One family of microdomains harbors the scaffolding flotillin protein FloA that selectively tethers proteins specialized in regulating cell envelope turnover and primary metabolism. A second population of microdomains containing the two scaffolding flotillins, FloA and FloT, arises exclusively at later stages of cell growth and specializes in adaptation of cells to stationary phase. Importantly, the diversification of membrane microdomains does not occur arbitrarily. We discovered that bacterial cells control the spatio-temporal remodeling of microdomains by restricting the activation of FloT expression to stationary phase. This regulation ensures a sequential assembly of functionally specialized membrane microdomains to strategically organize signaling networks at the right time during the lifespan of a bacterium. KW - membrane proteins KW - gene expression KW - bacillus subtilis KW - fluorescence microscopy KW - cell fusion KW - signal transduction KW - gene regulation KW - lipids Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125577 VL - 11 IS - 4 ER - TY - JOUR A1 - Rau, Markus A1 - Heindel, Tobias A1 - Unsleber, Sebastian A1 - Braun, Tristan A1 - Fischer, Julian A1 - Frick, Stefan A1 - Nauerth, Sebastian A1 - Schneider, Christian A1 - Vest, Gwenaelle A1 - Reitzenstein, Stephan A1 - Kamp, Martin A1 - Forchel, Alfred A1 - Höfling, Sven A1 - Weinfurter, Harald T1 - Free space quantum key distribution over 500 meters using electrically driven quantum dot single-photon sources-a proof of principle experiment JF - New Journal of Physics N2 - Highly efficient single-photon sources (SPS) can increase the secure key rate of quantum key distribution (QKD) systems compared to conventional attenuated laser systems. Here we report on a free space QKD test using an electrically driven quantum dot single-photon source (QD SPS) that does not require a separate laser setup for optical pumping and thus allows for a simple and compact SPS QKD system. We describe its implementation in our 500 m free space QKD system in downtown Munich. Emulating a BB84 protocol operating at a repetition rate of 125 MHz, we could achieve sifted key rates of 5-17 kHz with error ratios of 6-9% and g((2))(0)-values of 0.39-0.76. KW - QKD KW - electrically driven KW - free space KW - quantum dots KW - quantum key distribution Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116760 VL - 16 IS - 043003 ER - TY - THES A1 - Schneider, Markus T1 - Exhalatkondensat bei Gesunden und thorakal bestrahlten Patienten T1 - Breath Condensate in healthy persons and patients with therapeutic chest irradiation N2 - Die thorakale Strahlentherapie birgt stets das Risiko der Entstehung einer Pneumonitis, deren frühe Diagnose wichtig ist. Mit der Exhalat-Kondensat-Methode gelingt es, die alveoläre Oberfläche wenig invasiv und beliebig oft wiederholbar untersuchen zu können. Methodik, Variabilität der Exhalatparameter bei Gesunden, Unterschiede zwischen diesen und Patienten während einer thorakalen Strahlentherapie sollten untersucht, Zusammenhänge der Exhalatparameter mit Blutserumkonzentrationen von Total-Protein und TGF-beta; geklärt werden und die Eignung der Methode zur Früherkennung einer Strahlenpneumonitis geprüft werden. 14 gesunde Probanden (an drei aufeinander folgenden Messtagen) und 14 Patienten (bei 0 und 50Gy Gesamt-Energiedosis) wurden untersucht. Jeder atmete 15 Minuten lang am Jaeger ECoScreen; Exhalatmenge und Atemvolumen (V’E) wurden bestimmt. Bei den Probanden wurde am ersten Messtag, bei den Patienten beides Mal Blutserum abgenommen. Exhalat- und Serumproben wurden eingefroren und später auf TGF-beta; und Total-Protein untersucht. Die Untersuchungen waren problemlos durchzuführen; die Messung des V’E war allerdings umständlich. Eine Bestimmung der Masse des Exhalat-Kondensats ist genauer als die des Volumens. TGF-beta; konnte in keiner Kondensatprobe nachgewiesen werden, Total-Protein bei allen. Total-Protein und TGF-beta; ließen sich im Serum messen. Vier Patienten erkrankten an einer Pneumonitis, im Mittel 43,5 ±27 Tage nach Erhalt von 50Gy. Bei Gesunden bedeutet ein höheres V’E auch signifikant mehr Exhalat (p = 0,0004***); die Tag-zu-Tag-Variabilität aller Exhalatparameter war beträchtlich. Übungsphasen, weitere Standardisierungen und geeignete „Referenzkollektive“ sind für eine Etablierung der Methode unbedingt notwendig. Patienten höheren Körpergewichts (p = 0,0072**) und mit einem größerem Body-Mass-Index (BMI, p = 0,0095**) produzierten vor Therapie signifikant mehr Exhalat-Kondensat. Es fand sich bei den Älteren am zweiten Messtermin signifikant mehr Protein im Exhalat (p = 0,045*), dies ist als Alters- und / oder Krankheitsfolge zu werten (in beiden Teilkollektiven findet sich kein solcher Zusammenhang). Die Patienten hatten höhere Ausgangswerte aller drei Exhalatparameter als die Probanden. Bei den Gesunden fand sich infolge „Gewöhnung“ an die Messapparatur am zweiten Messtag weniger Exhalat und ein geringeres V’E. Die Patienten hatten vor Beginn der Therapie mehr Protein im Exhalat, was eine bei vielen vorbestehende alveoläre Schrankenstörung vermuten lässt. Die Patienten hatten stets mehr Protein im Exhalat als die Probanden, dieses stieg während der Therapie um das 1,7fache an; trotzdem ließ sich kein signifikanter Zusammenhang mit der Entwicklung einer Strahlenpneumonitis finden. Bei den Gesunden fanden sich bei jeweils höheren Ausgangswerten auch signifikant stärkere Abnahmen der Exhalatmenge (p = 0,025*) und des V’E (p = 0,040*) – es kommt also bei den „Gewöhnungseffekten“ auf die Zeitdauer des Messintervalls an. Mittelwerte aus mehreren Messungen trugen zu einer schärferen Abgrenzung der zwei Kollektive bei; bei jeweils n = 22 Personen pro Kollektiv wären mehr signifikante Unterschiede zu finden gewesen. Die Serumkonzentrationen von Protein und TGF-beta waren von den demographischen Daten unabhängig und hingen niemals voneinander ab. Die TGF-beta-Serumkonzentrationen der an Pneumonitis erkrankten Patienten nahmen im Laufe der Strahlentherapie im Durchschnitt um 32,9% ab, während sie sich bei den übrigen praktisch nicht änderten; wahrscheinlich handelt es sich hier um typische transiente Abfälle von TGF-beta. Bei den Probanden waren Serum- und Exhalatparameter unabhängig voneinander. Bei den Patienten war mehr Protein im Exhalat-Kondensat, wenn bei 0Gy mehr Serum-TGF-beta vorhanden war. Nach 50Gy war umso mehr Protein im Kondensat, je niedriger es im Serum war. Bei Patienten, die im Laufe der Therapie mehr Protein im Exhalat hatten, fand sich auch eine signifikant steigende Proteinkonzentration im Serum (p = 0,027*). Sinkt TGF-beta im Serum während der Therapie ab (eher steigendes Pneumonitis-Risiko in dieser Studie), dann steigt V’E (p = 0,0100*) und sinkt das Protein im Exhalat (p = 0,043*) signifikant. Bei 0Gy war der Protein-Quotient aus Exhalat und Serum bei den Patienten 1,3mal höher und stieg bis 50Gy um das 1,75fache auf das 2,28fache der Probanden-Ausgangswerte an. Ein hohes TGF-beta im Serum bei 0Gy ging mit einem signifikant steigenden V’E (p = 0,0067**) und sinkenden Protein im Exhalat (p = 0,012*) im Laufe der Therapie einher. Steigt Protein im Serum während der Therapie an, fand sich ein eher höheres V’E vor Beginn der Therapie. Waren Exhalatmenge und V’E vor Therapie eher hoch, stieg TGF-beta im Serum bis 50Gy eher an. N2 - - not available - KW - Exhalatkondensat KW - Totalprotein KW - Strahlentherapie KW - TGF beta KW - Pneumonitis KW - breath condensate KW - proteine KW - thoracic radiation KW - TGF beta KW - pneumonitis Y1 - 2004 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-10579 ER - TY - JOUR A1 - Lombardi, Jolina A1 - Mayer, Benjamin A1 - Semler, Elisa A1 - Anderl‐Straub, Sarah A1 - Uttner, Ingo A1 - Kassubek, Jan A1 - Diehl‐Schmid, Janine A1 - Danek, Adrian A1 - Levin, Johannes A1 - Fassbender, Klaus A1 - Fliessbach, Klaus A1 - Schneider, Anja A1 - Huppertz, Hans‐Jürgen A1 - Jahn, Holger A1 - Volk, Alexander A1 - Kornhuber, Johannes A1 - Landwehrmeyer, Bernhard A1 - Lauer, Martin A1 - Prudlo, Johannes A1 - Wiltfang, Jens A1 - Schroeter, Matthias L. A1 - Ludolph, Albert A1 - Otto, Markus T1 - Quantifying progression in primary progressive aphasia with structural neuroimaging JF - Alzheimer's & Dementia N2 - Introduction The term primary progressive aphasia (PPA) sums up the non‐fluent (nfv), the semantic (sv), and the logopenic (lv) variant. Up to now, there is only limited data available concerning magnetic resonance imaging volumetry to monitor disease progression. Methods Structural brain imaging and an extensive assessment were applied at baseline and up to 4‐year(s) follow‐up in 269 participants. With automated atlas‐based volumetry 56 brain regions were assessed. Atrophy progression served to calculate sample sizes for therapeutic trials. Results At baseline highest atrophy appeared in parts of the left frontal lobe for nfvPPA (–17%) and of the left temporal lobe for svPPA (–34%) and lvPPA (–24%). Severest progression within 1‐year follow‐up occurred in the basal ganglia in nfvPPA (–7%), in the hippocampus/amygdala in svPPA (–9%), and in (medial) temporal regions in lvPPA (–6%). Conclusion PPA presents as a left‐dominant, mostly gray matter sensitive disease with considerable atrophy at baseline that proceeds variant‐specific. KW - atlas‐based volumetry KW - disease progression KW - frontotemporal dementia KW - longitudinal magnetic resonance imaging KW - primary progressive aphasia KW - sample size calculation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262605 VL - 17 IS - 10 SP - 1595 EP - 1609 ER - TY - JOUR A1 - Tegtmeyer, Nicole A1 - Moodley, Yoshan A1 - Yamaoka, Yoshio A1 - Pernitzsch, Sandy Ramona A1 - Schmidt, Vanessa A1 - Traverso, Francisco Rivas A1 - Schmidt, Thomas P. A1 - Rad, Roland A1 - Yeoh, Khay Guan A1 - Bow, Ho A1 - Torres, Javier A1 - Gerhard, Markus A1 - Schneider, Gisbert A1 - Wessler, Silja A1 - Backert, Steffen T1 - Characterisation of worldwide Helicobacter pylori strains reveals genetic conservation and essentiality of serine protease HtrA JF - Molecular Microbiology N2 - HtrA proteases and chaperones exhibit important roles in periplasmic protein quality control and stress responses. The genetic inactivation of htrA has been described for many bacterial pathogens. However, in some cases such as the gastric pathogen Helicobacter pylori, HtrA is secreted where it cleaves the tumour-suppressor E-cadherin interfering with gastric disease development, but the generation of htrA mutants is still lacking. Here, we show that the htrA gene locus is highly conserved in worldwide strains. HtrA presence was confirmed in 992 H.pylori isolates in gastric biopsy material from infected patients. Differential RNA-sequencing (dRNA-seq) indicated that htrA is encoded in an operon with two subsequent genes, HP1020 and HP1021. Genetic mutagenesis and complementation studies revealed that HP1020 and HP1021, but not htrA, can be mutated. In addition, we demonstrate that suppression of HtrA proteolytic activity with a newly developed inhibitor is sufficient to effectively kill H.pylori, but not other bacteria. We show that Helicobacter htrA is an essential bifunctional gene with crucial intracellular and extracellular functions. Thus, we describe here the first microbe in which htrA is an indispensable gene, a situation unique in the bacterial kingdom. HtrA can therefore be considered a promising new target for anti-bacterial therapy. KW - Helicobacter pylori KW - cag pathogenicity island KW - Differential RNA-sequencing KW - epithelial cells KW - campylobacter jejuni infection Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190774 VL - 99 IS - 5 ER - TY - JOUR A1 - Derakhshani, Shaghayegh A1 - Kurz, Andreas A1 - Japtok, Lukasz A1 - Schumacher, Fabian A1 - Pilgram, Lisa A1 - Steinke, Maria A1 - Kleuser, Burkhard A1 - Sauer, Markus A1 - Schneider-Schaulies, Sibylle A1 - Avota, Elita T1 - Measles virus infection fosters dendritic cell motility in a 3D environment to enhance transmission to target cells in the respiratory epithelium JF - Frontiers in Immunology N2 - Transmission of measles virus (MV) from dendritic to airway epithelial cells is considered as crucial to viral spread late in infection. Therefore, pathways and effectors governing this process are promising targets for intervention. To identify these, we established a 3D respiratory tract model where MV transmission by infected dendritic cells (DCs) relied on the presence of nectin-4 on H358 lung epithelial cells. Access to recipient cells is an important prerequisite for transmission, and we therefore analyzed migration of MV-exposed DC cultures within the model. Surprisingly, enhanced motility toward the epithelial layer was observed for MV-infected DCs as compared to their uninfected siblings. This occurred independently of factors released from H358 cells indicating that MV infection triggered cytoskeletal remodeling associated with DC polarization enforced velocity. Accordingly, the latter was also observed for MV-infected DCs in collagen matrices and was particularly sensitive to ROCK inhibition indicating infected DCs preferentially employed the amoeboid migration mode. This was also implicated by loss of podosomes and reduced filopodial activity both of which were retained in MV-exposed uninfected DCs. Evidently, sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as produced in response to virus-infection in DCs contributed to enhanced velocity because this was abrogated upon inhibition of sphingosine kinase activity. These findings indicate that MV infection promotes a push-and-squeeze fast amoeboid migration mode via the SphK/S1P system characterized by loss of filopodia and podosome dissolution. Consequently, this enables rapid trafficking of virus toward epithelial cells during viral exit. KW - dendritic cell KW - cell migration KW - measles virus KW - 3D tissue model KW - sphingosine-1-phosphate Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201818 VL - 10 IS - 1294 ER - TY - JOUR A1 - Meir, Michael A1 - Kannapin, Felix A1 - Diefenbacher, Markus A1 - Ghoreishi, Yalda A1 - Kollmann, Catherine A1 - Flemming, Sven A1 - Germer, Christoph-Thomas A1 - Waschke, Jens A1 - Leven, Patrick A1 - Schneider, Reiner A1 - Wehner, Sven A1 - Burkard, Natalie A1 - Schlegel, Nicolas T1 - Intestinal epithelial barrier maturation by enteric glial cells is GDNF-dependent JF - International Journal of Molecular Sciences N2 - Enteric glial cells (EGCs) of the enteric nervous system are critically involved in the maintenance of intestinal epithelial barrier function (IEB). The underlying mechanisms remain undefined. Glial cell line-derived neurotrophic factor (GDNF) contributes to IEB maturation and may therefore be the predominant mediator of this process by EGCs. Using GFAP\(^{cre}\) x Ai14\(^{floxed}\) mice to isolate EGCs by Fluorescence-activated cell sorting (FACS), we confirmed that they synthesize GDNF in vivo as well as in primary cultures demonstrating that EGCs are a rich source of GDNF in vivo and in vitro. Co-culture of EGCs with Caco2 cells resulted in IEB maturation which was abrogated when GDNF was either depleted from EGC supernatants, or knocked down in EGCs or when the GDNF receptor RET was blocked. Further, TNFα-induced loss of IEB function in Caco2 cells and in organoids was attenuated by EGC supernatants or by recombinant GDNF. These barrier-protective effects were blunted when using supernatants from GDNF-deficient EGCs or by RET receptor blockade. Together, our data show that EGCs produce GDNF to maintain IEB function in vitro through the RET receptor. KW - enteric glial cells KW - neurotrophic factors KW - intestinal epithelial barrier KW - GDNF5 KW - RET6 KW - inflammatory bowel disease KW - enteric nervous system KW - gut barrier KW - intercellular junctions Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258913 SN - 1422-0067 VL - 22 IS - 4 ER -