Müller, Gerhard Anton

[["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Fibrogenesis & Tissue Repair"],["dc.bibliographiccitation.lastpage","10"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Girgert, Rainer"],["dc.contributor.author","Martin, Maria"],["dc.contributor.author","Kruegel, Jenny"],["dc.contributor.author","Miosge, Nicolai"],["dc.contributor.author","Temme, Johanna"],["dc.contributor.author","Eckes, Beate"],["dc.contributor.author","Müller, Gerhard-Anton"],["dc.contributor.author","Gross, Oliver"],["dc.date.accessioned","2019-07-09T11:52:48Z"],["dc.date.available","2019-07-09T11:52:48Z"],["dc.date.issued","2010"],["dc.description.abstract","Background: Integrins are important cellular receptors for collagens. Within the glomerulus, podocytes regulate the integrity of the glomerular basement membrane (GBM) by sensing the presence of collagen and regulating collagen IV synthesis. The present study evaluates the role of integrin a2 (ITGA2) in cell-matrix interaction. Methods and Results: ITGA2-deficient mice had normal renal function but moderate proteinuria and enhanced glomerular and tubulointerstitial matrix deposition. Electron microscopy demonstrated irregular podocyte-matrix interaction, causing pathological protrusions towards the urinary (podocyte) side of the GBM. These characteristic subepithelial bulges mimic the renal phenotype of mice, which are deficient in another collagen receptor, discoidin domain receptor (DDR)1. Using immunogold staining, ITGA2 expression was found to localize to the basolateral site of the podocyte foot processes. ITGA2-deficient mice overexpressed transforming growth factor (TGF)b and connective tissue growth factor (CTGF) compared with wild-type mice. Using in situ hybridization, tubular cells were found to be the primary site of TGFb synthesis and podocytes the source of CTGF in ITGA2- deficient mice. Conclusion: These findings support our hypothesis that both these collagen receptors (ITGA2 and DDR1) play a similar role within the kidney. Further, cell-matrix interaction via collagen receptors seems to be crucial for maintenance of normal GBM architecture and function. Targeting collagen receptors such as ITGA2 might be a new form of treatment for progressive fibrotic diseases."],["dc.identifier.doi","10.1186/1755-1536-3-19"],["dc.identifier.fs","575629"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6018"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60281"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/6905 but duplicate"],["dc.rights","Goescholar"],["dc.rights.access","openAccess"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Integrin a2-deficient mice provide insights into specific functions of collagen receptors in the kidney"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1325"],["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Lipphardt, Mark"],["dc.contributor.author","Dihazi, Hassan"],["dc.contributor.author","Müller, Gerhard A."],["dc.contributor.author","Goligorsky, Michael S."],["dc.date.accessioned","2019-07-09T11:45:55Z"],["dc.date.available","2019-07-09T11:45:55Z"],["dc.date.issued","2018"],["dc.description.abstract","Sirtuins (SIRT) are ubiquitous histone and protein deacetylases and a member of this family, SIRT1, is the best-studied one. Its functions in endothelial cells encompass branching angiogenesis, activation of endothelial nitric oxide synthase, regulation of proapoptotic and proinflammatory pathways, among others. Defective SIRT1 activity has been described in various cardiovascular, renal diseases and in aging-associated conditions. Therefore, understanding of SIRT1-deficient, endothelial dysfunctional phenotype has much to offer clinically. Here, we summarize recent studies by several investigative teams of the characteristics of models of global endothelial SIRT1 deficiency, the causes of facilitative development of fibrosis in these conditions, dissect the protein composition of the aberrant secretome of SIRT1-deficient endothelial cells and present several components of this aberrant secretome that are involved in fibrogenesis via activation of fibroblasts to myofibroblasts. These include ligands of Wnt and Notch pathways, as well as proteolytic fragments of glycocalyx core protein, syndecan-4. The latter finding is crucial for understanding the degradation of glycocalyx that accompanies SIRT1 deficiency. This spectrum of abnormalities associated with SIRT1 deficiency in endothelial cells is essential for understanding the origins and features of endothelial dysfunction in a host of cardiovascular and renal diseases."],["dc.identifier.doi","10.3389/fphys.2018.01325"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15344"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59337"],["dc.language.iso","en"],["dc.notes.intern","DeepGreen Import"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-042X"],["dc.relation.issn","1664-042X"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.subject.ddc","610"],["dc.title","Fibrogenic Secretome of Sirtuin 1-Deficient Endothelial Cells: Wnt, Notch and Glycocalyx Rheostat"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","56"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","European Journal of Medical Research"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Patschan, D."],["dc.contributor.author","Sugiarto, N."],["dc.contributor.author","Henze, E."],["dc.contributor.author","Mößner, R."],["dc.contributor.author","Mohr, J."],["dc.contributor.author","Müller, G. A."],["dc.contributor.author","Patschan, S."],["dc.date.accessioned","2019-07-09T11:50:09Z"],["dc.date.available","2019-07-09T11:50:09Z"],["dc.date.issued","2018"],["dc.description.abstract","BACKGROUND: Both psoriasis (Ps) and psoriasis arthritis (PsA) have been associated with increased cardiovascular risk. Also, both are characterized by increased neovascularization. Endothelial progenitor cells (EPCs) have been implicated in promoting vascular repair in ischemic diseases. The aim of the study was to correlate the EPC system with CV risk factors and with parameters of vascular stiffness in Ps and PsA. METHODS: Twenty-six healthy subjects, 30 patients with Ps, and 31 patients PsA were included in the study. eEPC regeneration was evaluated by a colony-forming assay, circulating eEPCs were measured by cytometric analysis. For vascular analysis, all subjects underwent quantification of pulse wave velocity (PWV) and augmentation index (AIX). RESULTS: Patients were categorized upon the duration of disease, severity of skin involvement (PASI-Ps), individual pain as reflected by the VAS (PsA), CRP values, and history of treatment with one or more biologicals. Regarding the eEPC system, no significant differences were observed between the respective categories. Correlation analyses between parameters of vascular stiffness (PWV and AIX) and patterns of colony formation/circulating eEPCs did not show any correlation at all. CONCLUSION: Parameters of vascular stiffness are not significantly deteriorated in Ps/PsA. Thus, pulse wave analysis may not be suitable for CVR assessment in certain autoimmune-mediated diseases. Regenerative activity of the eEPC system/circulating eEPC numbers are not altered in Ps/PsA. One may conclude that malfunctions of the eEPC are not substantially involved in perpetuating the micro-/macrovascular alterations in Ps/PsA."],["dc.identifier.doi","10.1186/s40001-018-0352-7"],["dc.identifier.pmid","30413175"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15871"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59712"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2047-783X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Early endothelial progenitor cells and vascular stiffness in psoriasis and psoriatic arthritis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e0199345"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PloS one"],["dc.bibliographiccitation.lastpage","e0199345"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Korsten, Peter"],["dc.contributor.author","Mavropoulou, Eirini"],["dc.contributor.author","Wienbeck, Susanne"],["dc.contributor.author","Ellenberger, David"],["dc.contributor.author","Patschan, Daniel"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Vasko, Radovan"],["dc.contributor.author","Tampe, Björn"],["dc.contributor.author","Müller, Gerhard A."],["dc.date.accessioned","2019-07-09T11:45:40Z"],["dc.date.available","2019-07-09T11:45:40Z"],["dc.date.issued","2018"],["dc.description.abstract","RATIONALE: Central venous catheter (CVC) placement is a standard procedure in critical care. Ultrasound guidance during placement is recommended by current guidelines, but there is no consensus on the best method for evaluating the correct CVC tip position. Recently, the \"rapid atrial swirl sign\" (RASS) has been investigated in a limited number of studies. OBJECTIVES: We performed a prospective diagnostic accuracy study of focused echocardiography for the evaluation of CVC tip position in our medical ICU and IMC units. METHODS: We performed a prospective diagnostic accuracy study in 100 patients admitted to the Intensive Care Unit and Intermediate Care Unit at our center. The first 10 subjects were assessed by one staff physician investigator (reference cohort), the remaining 90 patients by different residents (test cohort). All patients received a post-procedural chest radiograph (CXR) as gold standard. CVC placement was assessed with focused echocardiography performed by residents after a short training session. A rapid opacification of the right atrium (RASS) after injection of 10 mL of normal saline was regarded as \"positive\", flush after more than two seconds was defined as \"delayed\", no flush was a \"negative\" test result. MEASUREMENTS AND MAIN RESULTS: Overall sensitivity of the RASS was 100% (95% CI 73.54-100%), specificity was 94.32% (CI 87.24-98.13%). Positive and negative predictive values were 70.59% (CI 44.04-89.09%) and 100% (CI 95.65-100%), respectively. Median time for echocardiographic testing was 5 minutes (1-28) in the whole cohort, CXRs were available after 49.5 minutes (13-254). Interrater agreement of the RASS was 0.77 (Cohen's kappa), Measurement of CVC tip position was not different between two observers. Test characteristics were similar among differently experienced residents. CONCLUSIONS: Presence of the RASS by focused echocardiography showed excellent sensitivity and specificity and was equally performed by residents after minimal training. In patients with a positive RASS, routine CXR can be safely omitted, reducing time, costs and radiation exposure. A negative RASS should lead to a search for misplaced catheters. CLINICAL TRIAL REGISTRATION: The study was registered with www.clinicaltrials.gov (NCT02661607)."],["dc.identifier.doi","10.1371/journal.pone.0199345"],["dc.identifier.pmid","30011285"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15276"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59280"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","The \"rapid atrial swirl sign\" for assessing central venous catheters: Performance by medical residents after limited training."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0206786"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Životić, Maja"],["dc.contributor.author","Tampe, Björn"],["dc.contributor.author","Müller, Gerhard"],["dc.contributor.author","Müller, Claudia"],["dc.contributor.author","Lipkovski, Aleksandar"],["dc.contributor.author","Xu, Xingbo"],["dc.contributor.author","Nyamsuren, Gunsmaa"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Marković-Lipkovski, Jasmina"],["dc.date.accessioned","2019-07-09T11:50:17Z"],["dc.date.available","2019-07-09T11:50:17Z"],["dc.date.issued","2018"],["dc.description.abstract","Neural cell adhesion molecule (NCAM) and fibroblast growth factor receptor 1 (FGFR1) cross-talk have been involved in epithelial-to-mesenchymal transition (EMT) process during carcinogenesis. Since EMT also contributes to maladaptive repair and parenchymal damage during renal fibrosis, we became encouraged to explore the role of NCAM/FGFR1 signaling as initiating or driving forces of EMT program in cultured human proximal tubular epithelial cells (TECs). TECs stimulated with TGF-β1 (10ng/mL) was used as an established in vitro EMT model. TGF-β1 downstream effectors were detected in vitro, as well as in 50 biopsies of different human kidney diseases to explore their in vivo correlation. NCAM/FGFR1 signaling and its modulation by FGFR1 inhibitor PD173074 (100nM) were analyzed by light microscopy, immunolabeling, qRT-PCR and scratch assays. Morphological changes associated with EMT appeared 48h after TGF-ß1 treatment and was clearly apparent after 72 hours, followed by loss of CDH1 (encoding E-Cadherin) and transcriptional induction of SNAI1 (SNAIL), SNAI2 (SLUG), TWIST1, MMP2, MMP9, CDH2 (N-Cadherin), ITGA5 (integrin-α5), ITGB1 (integrin-β1), ACTA2 (α-SMA) and S100A4 (FSP1). Moreover, at the early stage of EMT program (24 hours upon TGF-β1 exposure), transcriptional induction of several NCAM isoforms along with FGFR1 was observed, implicating a mechanistic link between NCAM/FGFR1 signaling and induction of EMT. These assumptions were further supported by the inhibition of the EMT program after specific blocking of FGFR1 signaling by PD173074. Finally, there was evidence for an in vivo TGF-β1 pathway activation in diseased human kidneys and correlation with impaired renal excretory functions. Collectively, NCAM/FGFR1 signaling appears to be involved in the initial phase of TGF-ß1 initiated EMT which can be effectively suppressed by application of FGFR inhibitor."],["dc.identifier.doi","10.1371/journal.pone.0206786"],["dc.identifier.pmid","30383875"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15900"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59738"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Modulation of NCAM/FGFR1 signaling suppresses EMT program in human proximal tubular epithelial cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","H484"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","American Journal of Physiology. Heart and Circulatory Physiology"],["dc.bibliographiccitation.lastpage","H496"],["dc.bibliographiccitation.volume","314"],["dc.contributor.author","Lipphardt, Mark"],["dc.contributor.author","Song, Jong W"],["dc.contributor.author","Ratliff, Brian B"],["dc.contributor.author","Dihazi, Hassan"],["dc.contributor.author","Müller, Gerhard A"],["dc.contributor.author","Goligorsky, Michael S"],["dc.date.accessioned","2019-07-09T11:45:25Z"],["dc.date.available","2019-07-09T11:45:25Z"],["dc.date.issued","2018"],["dc.description.abstract","Syndecan-4 (Synd4) is a member of the membrane-spanning, glycocalyx-forming proteoglycan family. It has been suggested that Synd4 participates in renal fibrosis. We compared wild-type and fibrosis-prone endothelial sirtuin 1-deficient (Sirt1endo-/-) mice, the latter being a model of global endothelial dysfunction. We performed mass spectrometry analysis, which revealed that Synd4 was highly enriched in the secretome of renal microvascular endothelial cells obtained from Sirt1endo-/- mice upon stimulation with transforming growth factor-β1; notably, all detectable peptides were confined to the ectodomain of Synd4. Elevated Synd4 was due to enhanced NF-κB signaling in Sirt1endo-/- mice, while its shedding occurred as a result of oxidative stress in Sirt1 deficiency. Synd4 expression was significantly enhanced after unilateral ureteral obstruction compared with contralateral kidneys. Furthermore, hyperplasia of renal myofibroblasts accompanied by microvascular rarefaction and overexpression of Synd4 were detected in Sirt1endo-/- mice. The ectodomain of Synd4 acted as a chemoattractant for monocytes with higher levels of macrophages and higher expression levels of Synd4 in the extracellular matrix of Sirt1endo-/- mice. In vitro, ectodomain application resulted in generation of myofibroblasts from cultured renal fibroblasts, while in vivo, subcapsular injection of ectodomain increased interstitial fibrosis. Moreover, the endothelial glycocalyx was reduced in Sirt1endo-/- mice, highlighting the induction of Synd4 occurring in parallel with the depletion of its intact form and accumulation of its ectodomain in Sirt1endo-/- mice. On the basis of our experimental results, we propose that it is the Synd4 ectodomain per se that is partially responsible for fibrosis in unilateral ureteral obstruction, especially when it is combined with endothelial dysfunction. NEW & NOTEWORTHY Our findings suggest that endothelial dysfunction induces the expression of syndecan-4 via activation of the NF-κB pathway. Furthermore, we show that syndecan-4 is shed to a greater amount because of increased oxidative stress in dysfunctional endothelial cells and that the release of the syndecan-4 ectodomain leads to tubulointerstitial fibrosis."],["dc.identifier.doi","10.1152/ajpheart.00548.2017"],["dc.identifier.pmid","29101181"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15199"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59225"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1522-1539"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Endothelial dysfunction is a superinducer of syndecan-4: fibrogenic role of its ectodomain."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e000185"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Lupus Science & Medicine"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Korsten, Peter"],["dc.contributor.author","Patschan, Daniel"],["dc.contributor.author","Henze, Elvira"],["dc.contributor.author","Niewold, Timothy B."],["dc.contributor.author","Müller, Gerhard-Anton"],["dc.contributor.author","Patschan, Susann Andrea"],["dc.date.accessioned","2019-07-09T11:45:40Z"],["dc.date.available","2019-07-09T11:45:40Z"],["dc.date.issued","2016"],["dc.description.abstract","Patients with SLE display a significantly higher cardiovascular risk (CVR). Pulse wave velocity (PWV) has meanwhile been established as a reliable parameter of end-organ damage. Endothelial progenitor cells (EPCs) are critically involved in vascular repair under both physiological and pathological conditions. The aim of the study was to analyse PWV and the Vascular Augmentation Index (VAI) and EPC numbers/regeneration in a well-defined German SLE cohort. Thirty patients were included. Only two individuals displayed a PWV of above 10 m/s. There was no correlation between PWV percentiles and disease activity as reflected by the SLE Disease Activity Index. Neither EPC colonies nor percentages of circulating EPCs (CD133+/KDR+) correlated with PWV/VAI in a positive or negative manner. Thus, it can be questioned whether pulse wave analysis and/or EPC proliferation and circulating cell numbers are truly useful for CVR assessment in SLE."],["dc.identifier.doi","10.1136/lupus-2016-000185"],["dc.identifier.pmid","28176918"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15278"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59282"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2053-8790"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Dynamics of pulse wave velocity and vascular augmentation index in association with endothelial progenitor cells in SLE."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]