Krügel, Jenny

[["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","170"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Nature Reviews Nephrology"],["dc.bibliographiccitation.lastpage","178"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Kruegel, Jenny"],["dc.contributor.author","Rubel, Diana"],["dc.contributor.author","Gross, Oliver"],["dc.date.accessioned","2018-11-07T09:27:25Z"],["dc.date.available","2018-11-07T09:27:25Z"],["dc.date.issued","2013"],["dc.description.abstract","In 1927, Arthur C. Alport first published his description of a triad of symptoms in a family with hereditary congenital haemorrhagic nephritis, deafness and ocular changes. A few years after his death, this group of symptoms was renamed Alport syndrome. To this day, Alport syndrome still inevitably leads to end-stage renal disease and the need for renal replacement therapy, starting in young adulthood. During the past two decades, research into this rare disease has focused on the effects of mutations in collagen type IV and the role of changes in podocytes and the glomerular basement membrane that lead to early kidney fibrosis. Animal models of Alport syndrome also demonstrate the pathogenetic importance of interactions between podocytes and the extracellular matrix. Such models might also help researchers to answer basic questions about podocyte function and the development of fibrosis, and to develop new therapeutic approaches that might be of use in other kidney diseases. In this Review, we discuss the latest basic and clinical research on Alport syndrome, focusing on the roles of podocyte pathology and the extracellular matrix. We also highlight early diagnosis and treatment options for young patients with this disorder."],["dc.identifier.doi","10.1038/nrneph.2012.259"],["dc.identifier.isi","000316713800010"],["dc.identifier.pmid","23165304"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30531"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1759-5061"],["dc.title","Alport syndrome-insights from basic and clinical research"],["dc.type","review"],["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"]]