Miosge, Nicolai

[["dc.bibliographiccitation.firstpage","272"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cellular Signalling"],["dc.bibliographiccitation.lastpage","283"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Wallbach, Manuel"],["dc.contributor.author","Escobar, Jorge Duque"],["dc.contributor.author","Babaeikelishomi, Rohollah"],["dc.contributor.author","Stahnke, Marie-Jeannette"],["dc.contributor.author","Blume, Roland"],["dc.contributor.author","Schroeder, Sabine"],["dc.contributor.author","Kruegel, Jenny"],["dc.contributor.author","Maedler, Kathrin"],["dc.contributor.author","Kluth, Oliver"],["dc.contributor.author","Kehlenbach, Ralph H."],["dc.contributor.author","Miosge, Nicolai"],["dc.contributor.author","Oetjen, Elke"],["dc.date.accessioned","2018-11-07T10:16:38Z"],["dc.date.available","2018-11-07T10:16:38Z"],["dc.date.issued","2016"],["dc.description.abstract","The dual leucine zipper kinase DLK induces beta-cell apoptosis by inhibiting the transcriptional activity conferred by the beta-cell protective transcription factor cAMP response element binding protein CREB. This action might contribute to beta-cell loss and ultimately diabetes. Within its kinase domain DLK shares high homology with the mixed lineage kinase (MLK) 3, which is activated by tumor necrosis factor (TNF) alpha and interleukin (IL)-1 beta, known prediabetic signals. In the present study, the regulation of DLK in beta-cells by these cytokines was investigated. Both, TNF alpha and IL-1 beta induced the nuclear translocation of DLK. Mutations within a putative nuclear localization signal (NLS) prevented basal and cytokine-induced nuclear localization of DLK and binding to the importin receptor importin alpha, thereby demonstrating a functional NLS within DLK. DLK NLS mutants were catalytically active as they phosphorylated their down-stream kinase c-Jun N-terminal kinase to the same extent as DLK wild-type but did neither inhibit CREB-dependent gene transcription nor transcription conferred by the promoter of the anti-apoptotic protein BCL-xL In addition, the beta-cell apoptosis-inducing effect of DLK was severely diminished by mutation of its NLS. In a murine model of prediabetes, enhanced nuclear DLK was found. These data demonstrate that DLK exerts distinct functions, depending on its subcellular localization and thus provide a novel level of regulating DLK action. Furthermore, the prevention of the nuclear localization of DLK as induced by prediabetic signals with consecutive suppression of beta-cell apoptosis might constitute a novel target in the therapy of diabetes mellitus. (C) 2016 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.cellsig.2016.01.002"],["dc.identifier.isi","000371188000005"],["dc.identifier.pmid","26776303"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41072"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","1873-3913"],["dc.relation.issn","0898-6568"],["dc.title","Distinct functions of the dual leucine zipper kinase depending on its subcellular localization"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["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.firstpage","28"],["dc.bibliographiccitation.journal","Naunyn-Schmiedeberg s Archives of Pharmacology"],["dc.bibliographiccitation.lastpage","29"],["dc.bibliographiccitation.volume","379"],["dc.contributor.author","Wallbach, Manuel"],["dc.contributor.author","Kruegel, Jenny"],["dc.contributor.author","Miosge, Nicolai"],["dc.contributor.author","Oetjen, Elke"],["dc.date.accessioned","2018-11-07T08:31:17Z"],["dc.date.available","2018-11-07T08:31:17Z"],["dc.date.issued","2009"],["dc.identifier.isi","000266563200118"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17088"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.conference","50th Annual Meeting of the Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und Toxikologie"],["dc.relation.eventlocation","Mainz, GERMANY"],["dc.relation.issn","0028-1298"],["dc.title","Translocation of the mitogen-activated triple kinase DLK to the nucleus"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1077"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","HISTOLOGY AND HISTOPATHOLOGY"],["dc.bibliographiccitation.lastpage","1084"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Gersdorff, Nikolaus"],["dc.contributor.author","Otto, S."],["dc.contributor.author","Roediger, Matthias"],["dc.contributor.author","Kruegel, Jenny"],["dc.contributor.author","Miosge, Nicolai"],["dc.date.accessioned","2018-11-07T10:58:06Z"],["dc.date.available","2018-11-07T10:58:06Z"],["dc.date.issued","2007"],["dc.description.abstract","Nidogen- 1 and nidogen- 2 are major components of all basement membranes and are considered to function as link molecules between laminin and collagen type IV networks. Surprisingly, the knockout of one or both nidogens does not cause defects in all tissues or in all basement membranes. In this study, we have elucidated the appearance of the major basement membrane components in adult murine kidney lacking nidogen- 1, nidogen- 2, or both nidogens. To this end, we localized laminin- 111, perlecan, and collagen type IV in knockout mice, heterozygous (+/-) or homozygous (-/-) for the nidogen- 1 gene, the nidogen- 2 gene, or both nidogen genes with the help of light microscopic immunostaining. We also performed immunogold histochemistry to determine the occurrence of these molecules in the murine kidney at the ultrastructural level. The renal basement membranes of single knockout mice contained a similar distribution of laminin- 111, perlecan, and collagen type IV compared to heterozygous mice. In nidogen double- knockout animals, the basement membrane underlying the tubular epithelium was sometimes altered, giving a diffuse and thickened pattern, or was totally absent. The normal or thickened basement membrane of double- knockout mice also showed a similar distribution of laminin- 111, perlecan, and collagen type IV. The results indicate that the lack of nidogen- 1, nidogen- 2, or both nidogens, plays no crucial role in the occurrence and localization of laminin- 111, collagen type IV, and perlecan in murine tubular renal basement membranes."],["dc.identifier.isi","000247757300003"],["dc.identifier.pmid","17616934"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50403"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","F Hernandez"],["dc.relation.issn","0213-3911"],["dc.title","The absence of one or both nidogens does not alter basement membrane composition in adult murine kidney"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2879"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Cellular and Molecular Life Sciences"],["dc.bibliographiccitation.lastpage","2895"],["dc.bibliographiccitation.volume","67"],["dc.contributor.author","Kruegel, Jenny"],["dc.contributor.author","Miosge, Nicolai"],["dc.date.accessioned","2018-08-20T11:39:20Z"],["dc.date.available","2018-08-20T11:39:20Z"],["dc.date.issued","2010"],["dc.description.abstract","More than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration, and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized, opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components with a special emphasis on embryonic and adult stem cells and their niches."],["dc.identifier.doi","10.1007/s00018-010-0367-x"],["dc.identifier.pmid","20428923"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/4965"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15418"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","1420-9071"],["dc.relation.eissn","1420-682X"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Basement membrane components are key players in specialized extracellular matrices"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S205"],["dc.bibliographiccitation.issue","Suppl B"],["dc.bibliographiccitation.journal","Osteoarthritis and Cartilage"],["dc.bibliographiccitation.lastpage","S206"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Koelling, S."],["dc.contributor.author","Kruegel, J."],["dc.contributor.author","Lochte, T."],["dc.contributor.author","Miosge, N."],["dc.date.accessioned","2018-08-20T12:10:57Z"],["dc.date.available","2018-08-20T12:10:57Z"],["dc.date.issued","2006"],["dc.identifier.doi","10.1016/S1063-4584(07)60833-4"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15424"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.relation.eissn","1063-4584"],["dc.title","P389 Chrondrogenic Progenitorcells derived from late stages of Human Osteoarthirtis"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","859"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","HISTOLOGY AND HISTOPATHOLOGY"],["dc.bibliographiccitation.lastpage","868"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Roediger, Matthias"],["dc.contributor.author","Kruegel, Jenny"],["dc.contributor.author","Miosge, Nicolai"],["dc.contributor.author","Gersdorff, Nikolaus"],["dc.date.accessioned","2018-11-07T08:28:11Z"],["dc.date.available","2018-11-07T08:28:11Z"],["dc.date.issued","2009"],["dc.description.abstract","A major component of basement membranes (BMs) is perlecan, a five-domain heparan sulphate proteoglycan. During murine embryogenesis, nearly all BMs of mesenchymal origin express perlecan, and it is believed to participate in the supramolecular assembly of BMs. However, the distribution of perlecan in human embryonic and fetal tissues is widely unknown, except for cartilage anlagen of developing extremities and the fetal spine. Clinical syndromes, caused by perlecan-associated mutations or gene-defects, suggest its multifunctional involvement during human development. Here we reveal the immunohistochemistry of perlecan domains III and V during human development from gestational weeks (gw) 6 to 12 in basement membrane zones (BMZs) of the developing brain, nervous system, blood vessels, skin, lung, heart, kidney, liver, intestine and skeletal system. Interestingly, a difference in the distribution of the two perlecan domains was found in the endoneurium of ganglia. Domain III is strongly present from gw 6 onwards, while domain V shows attenuated expression at this stage and has been detected abundantly only from gw 8 onwards, possibly indicating vascularization of the endoneurium during this early stage. We found perlecan to be present particularly at those stages of human development where epithelial-mesenchymal interactions occur."],["dc.identifier.isi","000266407500007"],["dc.identifier.pmid","19475532"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16364"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","F Hernandez"],["dc.relation.issn","0213-3911"],["dc.title","Tissue distribution of perlecan domains III and V during embryonic and fetal human development"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","346"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Matrix Biology"],["dc.bibliographiccitation.lastpage","356"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Gross, Oliver"],["dc.contributor.author","Girgert, Rainer"],["dc.contributor.author","Beirowski, Bogdan"],["dc.contributor.author","Kretzler, Matthias"],["dc.contributor.author","Kang, Hee Gyung"],["dc.contributor.author","Kruegel, Jenny"],["dc.contributor.author","Miosge, Nicolai"],["dc.contributor.author","Busse, Ann-Christin"],["dc.contributor.author","Segerer, Stephan"],["dc.contributor.author","Vogel, Wolfgang F."],["dc.contributor.author","Mueller, Gerhard-Anton"],["dc.contributor.author","Weber, Manfred"],["dc.date.accessioned","2018-11-07T08:42:54Z"],["dc.date.available","2018-11-07T08:42:54Z"],["dc.date.issued","2010"],["dc.description.abstract","Alport syndrome is a hereditary type IV collagen disease leading to progressive renal fibrosis, hearing loss and ocular changes. End stage renal failure usually develops during adolescence. COL4A3-/- mice serve as an animal model for progressive renal scarring in Alport syndrome. The present study evaluates the role of Discoidin Domain Receptor 1 (DDR1) in cell-matrix interaction involved in pathogenesis of Alport syndrome including renal inflammation and fibrosis. DDR1/COL4A3 Double-knockouts were compared to COL4A3-/- mice with 50% or 100% expression of DDR1, wildtype controls and to DDR1-/- COL4A3+/+ controls for over 6 years. Double-knockouts lived 47% longer, mice with 50% DDR1 lived 29% longer and showed improved renal function (reduction in proteinuria and blood urea nitrogen) compared to animals with 100% DDR1 expression. Loss of DDR1 reduced proinflammtory, profibrotic cells via signaling of TGF beta, CTGF, NF kappa B and IL-6 and decreased deposition of extracellular matrix. Immunogold-staining and in-situ hybridisation identified podocytes as major players in DDR1-mediated fibrosis and inflammation within the kidney. In summary, glomerular epithelial cells (podocytes) express DDR1. Loss of DDR1-expression in the kidney delayed renal fibrosis and inflammation in hereditary type IV collagen disease. This supports our hypothesis that podocyte-matrix interaction via collagen receptors plays an important part in progression of renal fibrosis in Alport disease. The blockade of collagen-receptor DDR1 might serve as an important new therapeutic concept in progressive fibrotic and inflammatory diseases in the future. (C) 2010 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.matbio.2010.03.002"],["dc.identifier.isi","000280726400002"],["dc.identifier.pmid","20307660"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19817"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0945-053X"],["dc.title","Loss of collagen-receptor DDR1 delays renal fibrosis in hereditary type IV collagen disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","324"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cell Stem Cell"],["dc.bibliographiccitation.lastpage","335"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Koelling, Sebastian"],["dc.contributor.author","Kruegel, Jenny"],["dc.contributor.author","Irmer, Malte"],["dc.contributor.author","Path, Jan Ragnar"],["dc.contributor.author","Sadowski, Boguslawa"],["dc.contributor.author","Miro, Xavier"],["dc.contributor.author","Miosge, Nicolai"],["dc.date.accessioned","2018-11-07T08:30:48Z"],["dc.date.available","2018-11-07T08:30:48Z"],["dc.date.issued","2009"],["dc.description.abstract","The regeneration of diseased hyaline cartilage continues to be a great challenge, mainly because degeneration-caused either by major injury or by age-related processes-can overextend the tissue's self-renewal capacity. We show that repair tissue from human articular cartilage during the late stages of osteoarthritis harbors a unique progenitor cell population, termed chondrogenic progenitor cells (CPCs). These exhibit stem cell characteristics such as clonogenicity, multipotency, and migratory activity. The isolated CPCs, which exhibit a high chondrogenic potential, were shown to populate diseased tissue ex vivo. Moreover, downregulation of the osteogenic transcription factor runx-2 enhanced the expression of the chondrogenic transcription factor sox-9. This, in turn, increased the matrix synthesis potential of the CPCs without altering their migratory capacity. Our results offer new insights into the biology of progenitor cells in the context of diseased cartilage tissue. Our work may be relevant in the development of novel therapeutics for the later stages of osteoarthritis."],["dc.description.sponsorship","Deutsche Arthrose Stiftung; Medical Faculty, Goettingen University"],["dc.identifier.doi","10.1016/j.stem.2009.01.015"],["dc.identifier.isi","000265162700009"],["dc.identifier.pmid","19341622"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6060"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16977"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1934-5909"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Migratory Chondrogenic Progenitor Cells from Repair Tissue during the Later Stages of Human Osteoarthritis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","206"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Matrix Biology"],["dc.bibliographiccitation.lastpage","213"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Gerter, Regina"],["dc.contributor.author","Kruegel, Jenny"],["dc.contributor.author","Miosge, Nicolai"],["dc.date.accessioned","2018-08-20T11:28:05Z"],["dc.date.available","2018-08-20T11:28:05Z"],["dc.date.issued","2012"],["dc.description.abstract","Osteoarthritis is one of the most common musculo-skeletal diseases with a complex patholoy and a strong impact on cell biology, differentiation and migration behavior of mesenchymal stem cell-derived progenitor cells. In this review, we elucidate the influence of the pathologically altered extracellular matrix on progenitor cell behavior. Moreover, we discuss the modulation of progenitor cells especially of previously characterized chondrogenic progenitor cells (Koelling et al., 2009) in situ to enhance their regeneration potential. These options comprise the application of growth factors like fibroblast growth factor-2, a Runx-2 knock down and a contemporary anti-inflammatory therapy. This supports endogenous regeneration on behalf of the diseased osteoarthritic cartilage, which otherwise results mainly in an insufficient fibro-cartilaginous repair tissue. Furthermore, new results indicate a role of pericytes in osteoarthritis for these repair attempts. We discuss the biological mechanisms potentially leading to new therapeutic options in osteoarthritis to enhance regeneration in situ."],["dc.identifier.doi","10.1016/j.matbio.2012.01.007"],["dc.identifier.pmid","22266025"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15416"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1569-1802"],["dc.relation.eissn","0945-053X"],["dc.title","New insights into cartilage repair - The role of migratory progenitor cells in osteoarthritis"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]