Zeisberg, Michael

[["dc.bibliographiccitation.artnumber","3509"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.lastpage","15"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Xu, Xingbo"],["dc.contributor.author","Tan, Xiaoying"],["dc.contributor.author","Tampe, Björn"],["dc.contributor.author","Wilhelmi, Tim"],["dc.contributor.author","Hulshoff, Melanie S."],["dc.contributor.author","Saito, Shoji"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Kalluri, Raghu"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.contributor.author","Zeisberg, Michael"],["dc.date.accessioned","2019-02-27T12:52:18Z"],["dc.date.available","2019-02-27T12:52:18Z"],["dc.date.issued","2018"],["dc.description.abstract","While suppression of specific genes through aberrant promoter methylation contributes to different diseases including organ fibrosis, gene-specific reactivation technology is not yet available for therapy. TET enzymes catalyze hydroxymethylation of methylated DNA, reactivating gene expression. We here report generation of a high-fidelity CRISPR/Cas9-based gene-specific dioxygenase by fusing an endonuclease deactivated high-fidelity Cas9 (dHFCas9) to TET3 catalytic domain (TET3CD), targeted to specific genes by guiding RNAs (sgRNA). We demonstrate use of this technology in four different anti-fibrotic genes in different cell types in vitro, among them RASAL1 and Klotho, both hypermethylated in kidney fibrosis. Furthermore, in vivo lentiviral delivery of the Rasal1-targeted fusion protein to interstitial cells and of the Klotho-targeted fusion protein to tubular epithelial cells each results in specific gene reactivation and attenuation of fibrosis, providing gene-specific demethylating technology in a disease model."],["dc.identifier.doi","10.1038/s41467-018-05766-5"],["dc.identifier.pmid","30158531"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15605"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57643"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/225"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C01: Epigenetische Kontrolle der Herzfibrose"],["dc.relation","SFB 1002 | D03: ENPP3-vermittelter Phosphat-Metabolismus bei der Herzfibrose"],["dc.relation.issn","2041-1723"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG E. Zeisberg (Kardiales Stroma)"],["dc.relation.workinggroup","RG M. Zeisberg (Renale Fibrogenese)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","High-fidelity CRISPR/Cas9- based gene-specific hydroxymethylation rescues gene expression and attenuates renal fibrosis"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","19"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","EBioMedicine"],["dc.bibliographiccitation.lastpage","36"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Tampe, Björn"],["dc.contributor.author","Tampe, Desiree"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.contributor.author","Müller, Gerhard A."],["dc.contributor.author","Bechtel-Walz, Wibke"],["dc.contributor.author","Koziolek, Michael"],["dc.contributor.author","Kalluri, Raghu"],["dc.contributor.author","Zeisberg, Michael"],["dc.date.accessioned","2019-02-27T10:29:15Z"],["dc.date.available","2019-02-27T10:29:15Z"],["dc.date.issued","2015"],["dc.description.abstract","Progression of chronic kidney disease remains a principal problem in clinical nephrology and there is a pressing need for novel therapeutics and biomarkers. Aberrant promoter CpG island methylation and subsequent transcriptional silencing of specific genes have emerged as contributors to progression of chronic kidney disease. Here, we report that transcriptional silencing of the Ras-GTP suppressor RASAL1 contributes causally to progression of kidney fibrosis and we identified that circulating methylated RASAL1 promoter DNA fragments in peripheral blood correspond with levels of intrarenal levels of RASAL1 promoter methylation and degree of fibrosis in kidney biopsies, enabling non-invasive longitudinal analysis of intrarenal CpG island methylation. Retrospective analysis of patients with hypertensive nephrosclerosis revealed that circulating methylated RASAL1 promoter DNA fragments in peripheral blood decrease with Dihydralazine treatment in patients with hypertensive nephrosclerosis, and provided evidence that low-dose Dihydralazine delays decline of excretory kidney function, whereas Dihydralazine at standard doses had no protective effect. We demonstrate that the protective effect of Dihydralazine is due to induction of endogenous Tet3/Tdg-mediated DNA-de-methylation activity reversing aberrant promoter CpG island methylation, while HIF1α induction at standard doses counterbalances its protective activity. We conclude that RASAL1 promoter methylation is a therapeutic target and a biomarker of renal fibrosis. Our study suggests therapeutic use of low-dose Dihydralazine in patients with chronic kidney disease and fibrosis deserves further consideration."],["dc.identifier.doi","10.1016/j.ebiom.2014.11.005"],["dc.identifier.pmid","25717475"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11368"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57639"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/62"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C01: Epigenetische Kontrolle der Herzfibrose"],["dc.relation.issn","2352-3964"],["dc.relation.workinggroup","RG E. Zeisberg (Kardiales Stroma)"],["dc.relation.workinggroup","RG M. Zeisberg (Renale Fibrogenese)"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Induction of Tet3-dependent Epigenetic Remodeling by Low-dose Hydralazine Attenuates Progression of Chronic Kidney Disease"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","942"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Disease models & mechanisms"],["dc.bibliographiccitation.lastpage","951"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Duncan, Michael B."],["dc.contributor.author","Yang, Changqing"],["dc.contributor.author","Tanjore, Harikrishna"],["dc.contributor.author","Boyle, Patrick M."],["dc.contributor.author","Keskin, Doruk"],["dc.contributor.author","Sugimoto, Hikaru"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Olsen, Bjorn R."],["dc.contributor.author","Kalluri, Raghu"],["dc.date.accessioned","2019-07-09T11:40:07Z"],["dc.date.available","2019-07-09T11:40:07Z"],["dc.date.issued","2013-07-01"],["dc.description.abstract","The regenerative response to drug- and toxin-induced liver injury induces changes to the hepatic stroma, including the extracellular matrix. Although the extracellular matrix is known to undergo changes during the injury response, its impact on maintaining hepatocyte function and viability in this process remains largely unknown. We demonstrate that recovery from toxin-mediated injury is impaired in mice deficient in a key liver extracellular matrix molecule, type XVIII collagen, and results in rapid death. The type-XVIII-collagen-dependent response to liver injury is mediated by survival signals induced by α1β1 integrin, integrin linked kinase and the Akt pathway, and mice deficient in either α1β1 integrin or hepatocyte integrin linked kinase also succumb to toxic liver injury. These findings demonstrate that type XVIII collagen is an important functional component of the liver matrix microenvironment and is crucial for hepatocyte survival during injury and stress."],["dc.identifier.doi","10.1242/dmm.011577"],["dc.identifier.fs","603312"],["dc.identifier.pmid","23580202"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10675"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58095"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1754-8411"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Carbon Tetrachloride"],["dc.subject.mesh","Cell Death"],["dc.subject.mesh","Collagen Type XVIII"],["dc.subject.mesh","Extracellular Matrix"],["dc.subject.mesh","Gene Expression Regulation"],["dc.subject.mesh","Hepatocytes"],["dc.subject.mesh","Integrin alpha1beta1"],["dc.subject.mesh","Liver"],["dc.subject.mesh","Liver Diseases"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Protein Binding"],["dc.subject.mesh","Signal Transduction"],["dc.subject.mesh","Survival Analysis"],["dc.subject.mesh","Transforming Growth Factor beta"],["dc.title","Type XVIII collagen is essential for survival during acute liver injury in mice."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","544"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Nature Medicine"],["dc.bibliographiccitation.lastpage","U75"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Bechtel, Wibke"],["dc.contributor.author","McGoohan, Scott"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.contributor.author","Mueller, Georg Anton"],["dc.contributor.author","Kalbacher, Hubert"],["dc.contributor.author","Salant, David J."],["dc.contributor.author","Mueller, Claudia A."],["dc.contributor.author","Kalluri, Raghu"],["dc.contributor.author","Zeisberg, Michael"],["dc.date.accessioned","2018-11-07T08:43:42Z"],["dc.date.available","2018-11-07T08:43:42Z"],["dc.date.issued","2010"],["dc.description.abstract","Fibrogenesis is a pathological wound repair process that fails to cease, even when the initial insult has been removed. Fibroblasts are principal mediators of fibrosis, and fibroblasts from fibrotic tissues fail to return to their quiescent stage, including when cultured in vitro. In a search for underlying molecular mechanisms, we hypothesized that this perpetuation of fibrogenesis is caused by epigenetic modifications. We demonstrate here that hypermethylation of RASAL1, encoding an inhibitor of the Ras oncoprotein, is associated with the perpetuation of fibroblast activation and fibrogenesis in the kidney. RASAL1 hypermethylation is mediated by the methyltransferase Dnmt1 in renal fibrogenesis, and kidney fibrosis is ameliorated in Dnmt1(+/-) heterozygous mice. These studies demonstrate that epigenetic modifications may provide a molecular basis for perpetuated fibroblast activation and fibrogenesis in the kidney."],["dc.identifier.doi","10.1038/nm.2135"],["dc.identifier.isi","000277394700032"],["dc.identifier.pmid","20418885"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6180"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20036"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1078-8956"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Methylation determines fibroblast activation and fibrogenesis in the kidney"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]