Tampe, Björn

[["dc.bibliographiccitation.artnumber","208"],["dc.bibliographiccitation.journal","Frontiers in Medicine"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Korsten, Peter"],["dc.contributor.author","Müller, Gerhard A."],["dc.contributor.author","Rademacher, Jan-Gerd"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Tampe, Björn"],["dc.date.accessioned","2019-09-24T08:03:09Z"],["dc.date.available","2019-09-24T08:03:09Z"],["dc.date.issued","2019"],["dc.description.abstract","Raynaud's phenomenon (RP) is almost universally present in patients with Systemic Sclerosis (SSc). RP represents a generalized vasculopathy and potentially lead to digital ulcers (DU), which may be complicated by superinfection, tissue necrosis, and limb loss. We report the analysis of an extracorporeal procedure in a 36-year-old female patient with diffuse SSc with refractory RP and DU despite treatment with diltiazem, candesartan, sildenafil, and intravenous iloprost. We performed rheopheresis (RheoP), a variant of double-filtration plasmapheresis, as a potential new treatment option for refractory patients despite optimal medical therapy. We performed two RheoP per week every 4 weeks for a total of 3 months. Clinical improvement in DU healing occurred with no adverse events directly related to the treatment. While there was no reduction in the number of Raynaud attacks with RheoP, a significant reduction of the duration of attacks from a median of 15 (5–45, 95% CI 10–15) to 7 (3–30, 95% CI 6–10) minutes with an improvement of the Raynaud Condition Score (RCS) improved from 4 to 2. In conclusion, RheoP is a feasible and potentially beneficial treatment modality in patients with refractory RP and DU. We propose that RheoP should be investigated in a larger number of patients in a clinical trial setting."],["dc.identifier.doi","10.3389/fmed.2019.00208"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16392"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62449"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2296-858X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Rheopheresis for Digital Ulcers and Raynaud's Phenomenon in Systemic Sclerosis Refractory to Conventional Treatments"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","998"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Nature Medicine"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Lovisa, Sara"],["dc.contributor.author","LeBleu, Valerie S."],["dc.contributor.author","Tampe, Bjorn"],["dc.contributor.author","Sugimoto, Hikaru"],["dc.contributor.author","Vadnagara, Komal"],["dc.contributor.author","Carstens, Julienne L."],["dc.contributor.author","Wu, Chia-Chin"],["dc.contributor.author","Hagos, Yohannes"],["dc.contributor.author","Burckhardt, Birgitta-Christina"],["dc.contributor.author","Pentcheva-Hoang, Tsvetelina"],["dc.contributor.author","Nischal, Hersharan"],["dc.contributor.author","Allison, James P."],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Kalluri, Raghu"],["dc.date.accessioned","2018-11-07T09:52:34Z"],["dc.date.available","2018-11-07T09:52:34Z"],["dc.date.issued","2015"],["dc.description.abstract","Kidney fibrosis is marked by an epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells (TECs). Here we find that, during renal fibrosis, TECs acquire a partial EMT program during which they remain associated with their basement membrane and express markers of both epithelial and mesenchymal cells. The functional consequence of the EMT program during fibrotic injury is an arrest in the G2 phase of the cell cycle and lower expression of several solute and solvent transporters in TECs. We also found that transgenic expression of either Twist1 (encoding twist family bHLH transcription factor 1, known as Twist) or Snai1 (encoding snail family zinc finger 1, known as Snail) expression is sufficient to promote prolonged TGF-beta 1-induced G2 arrest of TECs, limiting the cells' potential for repair and regeneration. In mouse models of experimentally induced renal fibrosis, conditional deletion of Twist1 or Snai1 in proximal TECs resulted in inhibition of the EMT program and the maintenance of TEC integrity, while also restoring cell proliferation, dedifferentiation-associated repair and regeneration of the kidney parenchyma and attenuating interstitial fibrosis. Thus, inhibition of the EMT program in TECs during chronic renal injury represents a potential anti-fibrosis therapy."],["dc.identifier.doi","10.1038/nm.3902"],["dc.identifier.isi","000360961300012"],["dc.identifier.pmid","26236991"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36152"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1546-170X"],["dc.relation.issn","1078-8956"],["dc.title","Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2687"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","American Journal Of Pathology"],["dc.bibliographiccitation.lastpage","2698"],["dc.bibliographiccitation.volume","184"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Tampe, Bjoern"],["dc.contributor.author","LeBleu, Valerie S."],["dc.contributor.author","Tampe, Desiree"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.contributor.author","Kalluri, Raghu"],["dc.date.accessioned","2018-11-07T09:34:44Z"],["dc.date.available","2018-11-07T09:34:44Z"],["dc.date.issued","2014"],["dc.description.abstract","Thrombospondin-1 (TSP1) is a multifunctional matricellular protein known to promote progression of chronic kidney disease. To gain insight into the underlying mechanisms through which TSP1 accelerates chronic kidney disease, we compared disease progression in Col4a3 knockout (K0) mice, which develop spontaneous kidney failure, with that of Col4a3;Tsp1 double-knockout (DK0) mice. Decline of excretory renal function was significantly delayed in the absence of TSP1. Although Col4a3;Tsp1 DK0 mice did progress toward end-stage renal failure, their kidneys exhibited distinct histopathological lesions, compared with creatinine level- matched Col4a3 K0 mice. Although kidneys of both Col4a3 K0 and Col4a3;Tsp1 DK0 mice exhibited a widened tubulointerstitium, predominant lesions in Col4a3 K0 kidneys were collagen deposition and fibroblast accumulation, whereas in Col4a3;Tsp1 DK0 kidney inflammation was predominant, with less collagen deposition. Altered disease progression correlated with impaired activation of transforming growth factor-beta 1 (TGF-beta 1) in vivo and in vitro in the absence of TSP1. In summary, our findings suggest that TSP1 contributes to progression of chronic kidney disease by catalyzing activation of latent TGF-beta 1, resulting in promotion of a fibroproliferative response over an inflammatory response. Furthermore, the findings suggest that fibro-proliferative and inflammatory lesions are independent entities, both of which contribute to decline of renal function."],["dc.identifier.doi","10.1016/j.ajpath.2014.06.014"],["dc.identifier.isi","000342276800010"],["dc.identifier.pmid","25111226"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32238"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/79"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C01: Epigenetische Kontrolle der Herzfibrose"],["dc.relation.issn","1525-2191"],["dc.relation.issn","0002-9440"],["dc.relation.workinggroup","RG E. Zeisberg (Kardiales Stroma)"],["dc.relation.workinggroup","RG M. Zeisberg (Renale Fibrogenese)"],["dc.title","Thrombospondin-1 Deficiency Causes a Shift from Fibroproliferative to Inflammatory Kidney Disease and Delays Onset of Renal Failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2014"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Tampe, Désirée"],["dc.contributor.author","Schridde, Laura"],["dc.contributor.author","Korsten, Peter"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Hakroush, Samy"],["dc.contributor.author","Tampe, Björn"],["dc.date.accessioned","2021-10-01T09:58:23Z"],["dc.date.available","2021-10-01T09:58:23Z"],["dc.date.issued","2021"],["dc.description.abstract","Kidney fibrosis is a common manifestation and hallmark of a wide variety of chronic kidney disease (CKD) that appears in different morphological patterns, suggesting distinct pathogenic causes. Broad macroscopically visible scars are the sequelae of severe focal injury and complete parenchymal destruction, reflecting a wound healing response as a consequence of infarction. In the kidney, chronic glomerular injury leads to atrophy of the corresponding tubule, degeneration of this specific nephron, and finally interstitial fibrosis/tubular atrophy (IF/TA). Compared to this glomerulus-induced focal replacement scar, diffuse fibrosis independent of tubular atrophy appears to be a different pathogenic process. Kidney fibrosis appears to develop in a compartment-specific manner, but whether focal and diffuse fibrosis has distinct characteristics associated with other glomerular or tubulointerstitial lesions remains elusive. In the present study, we aimed to analyze renal fibrotic patterns related to renal lesions, which directly contribute to renal fibrogenesis, to unravel fibrotic patterns and manifestations upon damage to distinct renal compartments. Patterns of kidney fibrosis were analyzed in experimental models of CKD and various renal pathologies in correlation with histopathological and ultrastructural findings. After the induction of isolated crescentic glomerulonephritis (GN) in nephrotoxic serum-nephritis (NTN), chronic glomerular damage resulted in predominantly focal fibrosis adjacent to atrophic tubules. By contrast, using unilateral ureteral obstruction (UUO) as a model of primary injury to the tubulointerstitial compartment revealed diffuse fibrosis as the predominant pattern of chronic lesions. Finally, folic acid-induced nephropathy (FAN) as a model of primary tubular injury with consecutive tubular atrophy independent of chronic glomerular damage equally induced predominant focal IF/TA. By analyzing several renal pathologies, our data also suggest that focal and diffuse fibrosis appear to contribute as chronic lesions in the majority of human renal disease, mainly being present in antineutrophil cytoplasmic antibody (ANCA)-associated GN, lupus nephritis, and IgA nephropathy (IgAN). Focal IF/TA correlated with glomerular damage and irreversible injury to nephrons, whereas diffuse fibrosis in ANCA GN was associated explicitly with interstitial inflammation independent of glomerular damage and nephron loss. Ultrastructural analysis of focal IF/TA versus diffuse fibrosis revealed distinct matrix compositions, further supported by different collagen signatures in transcriptome datasets. With regard to long-term renal outcome, only the extent of focal IF/TA correlated with the development of end-stage kidney disease (ESKD) in ANCA GN. In contrast, diffuse kidney fibrosis did not associate with the long-term renal outcome. In conclusion, we here provide evidence that a focal pattern of kidney fibrosis seems to be associated with nephron loss and replacement scarring. In contrast, a diffuse pattern of kidney fibrosis appears to result from primary interstitial inflammation and injury."],["dc.description.abstract","Kidney fibrosis is a common manifestation and hallmark of a wide variety of chronic kidney disease (CKD) that appears in different morphological patterns, suggesting distinct pathogenic causes. Broad macroscopically visible scars are the sequelae of severe focal injury and complete parenchymal destruction, reflecting a wound healing response as a consequence of infarction. In the kidney, chronic glomerular injury leads to atrophy of the corresponding tubule, degeneration of this specific nephron, and finally interstitial fibrosis/tubular atrophy (IF/TA). Compared to this glomerulus-induced focal replacement scar, diffuse fibrosis independent of tubular atrophy appears to be a different pathogenic process. Kidney fibrosis appears to develop in a compartment-specific manner, but whether focal and diffuse fibrosis has distinct characteristics associated with other glomerular or tubulointerstitial lesions remains elusive. In the present study, we aimed to analyze renal fibrotic patterns related to renal lesions, which directly contribute to renal fibrogenesis, to unravel fibrotic patterns and manifestations upon damage to distinct renal compartments. Patterns of kidney fibrosis were analyzed in experimental models of CKD and various renal pathologies in correlation with histopathological and ultrastructural findings. After the induction of isolated crescentic glomerulonephritis (GN) in nephrotoxic serum-nephritis (NTN), chronic glomerular damage resulted in predominantly focal fibrosis adjacent to atrophic tubules. By contrast, using unilateral ureteral obstruction (UUO) as a model of primary injury to the tubulointerstitial compartment revealed diffuse fibrosis as the predominant pattern of chronic lesions. Finally, folic acid-induced nephropathy (FAN) as a model of primary tubular injury with consecutive tubular atrophy independent of chronic glomerular damage equally induced predominant focal IF/TA. By analyzing several renal pathologies, our data also suggest that focal and diffuse fibrosis appear to contribute as chronic lesions in the majority of human renal disease, mainly being present in antineutrophil cytoplasmic antibody (ANCA)-associated GN, lupus nephritis, and IgA nephropathy (IgAN). Focal IF/TA correlated with glomerular damage and irreversible injury to nephrons, whereas diffuse fibrosis in ANCA GN was associated explicitly with interstitial inflammation independent of glomerular damage and nephron loss. Ultrastructural analysis of focal IF/TA versus diffuse fibrosis revealed distinct matrix compositions, further supported by different collagen signatures in transcriptome datasets. With regard to long-term renal outcome, only the extent of focal IF/TA correlated with the development of end-stage kidney disease (ESKD) in ANCA GN. In contrast, diffuse kidney fibrosis did not associate with the long-term renal outcome. In conclusion, we here provide evidence that a focal pattern of kidney fibrosis seems to be associated with nephron loss and replacement scarring. In contrast, a diffuse pattern of kidney fibrosis appears to result from primary interstitial inflammation and injury."],["dc.description.sponsorship","Georg-August-Universität Göttingen"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.3390/cells10082014"],["dc.identifier.pii","cells10082014"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/90053"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-469"],["dc.publisher","MDPI"],["dc.relation.eissn","2073-4409"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Different Patterns of Kidney Fibrosis Are Indicative of Injury to Distinct Renal Compartments"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","810"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Nature Medicine"],["dc.bibliographiccitation.lastpage","811"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Sugimoto, Hikaru"],["dc.contributor.author","LeBleu, Valerie S."],["dc.contributor.author","Bosukonda, Dattatreyamurty"],["dc.contributor.author","Keck, Peter"],["dc.contributor.author","Taduri, Gangadhar"],["dc.contributor.author","Bechtel, Wibke"],["dc.contributor.author","Okada, Hirokazu"],["dc.contributor.author","Carlson, William"],["dc.contributor.author","Bey, Philippe"],["dc.contributor.author","Rusckowski, Mary"],["dc.contributor.author","Tampe, Bjoern"],["dc.contributor.author","Tampe, Desiree"],["dc.contributor.author","Kanasaki, Keizo"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Kalluri, Raghu"],["dc.date.accessioned","2018-11-07T09:23:08Z"],["dc.date.available","2018-11-07T09:23:08Z"],["dc.date.issued","2013"],["dc.identifier.doi","10.1038/nm.3081"],["dc.identifier.isi","000321557700014"],["dc.identifier.pmid","23836214"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29512"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1078-8956"],["dc.title","Regarding the mechanism of action of a proposed peptide agonist of the bone morphogenetic protein receptor activin-like kinase 3 Reply"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]

[["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","157"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Kidney International"],["dc.bibliographiccitation.lastpage","176"],["dc.bibliographiccitation.volume","91"],["dc.contributor.author","Tampe, Björn"],["dc.contributor.author","Steinle, Ulrike"],["dc.contributor.author","Tampe, Désirée"],["dc.contributor.author","Carstens, Julienne L."],["dc.contributor.author","Korsten, Peter"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.contributor.author","Müller, Gerhard A."],["dc.contributor.author","Kalluri, Raghu"],["dc.contributor.author","Zeisberg, Michael"],["dc.date.accessioned","2020-05-04T07:22:12Z"],["dc.date.available","2020-05-04T07:22:12Z"],["dc.date.issued","2017"],["dc.description.abstract","Acute kidney injury (AKI) and progressive chronic kidney disease (CKD) are intrinsically tied syndromes. In this regard, the acutely injured kidney often does not achieve its full regenerative capacity and AKI directly transitions into progressive CKD associated with tubulointerstitial fibrosis. Underlying mechanisms of such AKI-to-CKD progression are still incompletely understood and specific therapeutic interventions are still elusive. Because epigenetic modifications play a role in maintaining tissue fibrosis, we used a murine model of ischemia-reperfusion injury to determine whether aberrant promoter methylation of RASAL1 contributes causally to the switch between physiological regeneration and tubulointerstitial fibrogenesis, a hallmark of AKI-to-CKD progression. It is known that the antihypertensive drug hydralazine has demethylating activity, and that its optimum demethylating activity occurs at concentrations below blood pressure-lowering doses. Administration of low-dose hydralazine effectively induced expression of hydroxylase TET3, which catalyzed RASAL1 hydroxymethylation and subsequent RASAL1 promoter demethylation. Hydralazine-induced CpG promoter demethylation subsequently attenuated renal fibrosis and preserved excretory renal function independent of its blood pressure-lowering effects. In comparison, RASAL1 demethylation and inhibition of tubulointerstitial fibrosis was not detected upon administration of the angiotensin-converting enzyme inhibitor Ramipril in this model. Thus, RASAL1 promoter methylation and subsequent transcriptional RASAL1 suppression plays a causal role in AKI-to-CKD progression."],["dc.identifier.doi","10.1016/j.kint.2016.07.042"],["dc.identifier.pmid","27692563"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/64543"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/307"],["dc.language.iso","en"],["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.eissn","1523-1755"],["dc.relation.issn","0085-2538"],["dc.relation.workinggroup","RG E. Zeisberg (Kardiales Stroma)"],["dc.relation.workinggroup","RG M. Zeisberg (Renale Fibrogenese)"],["dc.title","Low-dose hydralazine prevents fibrosis in a murine model of acute kidney injury-to-chronic kidney disease progression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1407"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Missbach-Guentner, Jeannine"],["dc.contributor.author","Pinkert-Leetsch, Diana"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Ufartes, Roser"],["dc.contributor.author","Hornung, Daniel"],["dc.contributor.author","Tampe, Bjoern"],["dc.contributor.author","Zeisberg, Michael"],["dc.contributor.author","Alves, Frauke"],["dc.date.accessioned","2019-07-09T11:45:05Z"],["dc.date.available","2019-07-09T11:45:05Z"],["dc.date.issued","2018"],["dc.description.abstract","The increasing number of patients with end stage chronic kidney disease not only calls for novel therapeutics but also for pioneering research using convincing preclinical disease models and innovative analytical techniques. The aim of this study was to introduce a virtual histology approach using micro computed tomography (µCT) for the entire murine kidney in order to close the gap between single slice planar histology and a 3D high resolution dataset. An ex vivo staining protocol based on phosphotungstic acid diffusion was adapted to enhance renal soft tissue x-ray attenuation. Subsequent CT scans allowed (i) the detection of the renal cortex, medulla and pelvis in greater detail, (ii) the analysis of morphological alterations, (iii) the quantification of the volume as well as the radio-opacity of these portions and (iv) the quantification of renal fibrotic remodeling based on altered radio-opacity using the unilateral ureteral obstruction model. Thus, virtual histology based on PTA contrast enhanced CT will in future help to refine the outcome of preclinical research on kidney associated murine disease models."],["dc.identifier.doi","10.1038/s41598-018-19773-5"],["dc.identifier.pmid","29362427"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15031"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59157"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","3D virtual histology of murine kidneys -high resolution visualization of pathological alterations by micro computed tomography."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","24075"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Nyamsuren, Gunsmaa"],["dc.contributor.author","Rapp, Gregor"],["dc.contributor.author","Dihazi, Hassan"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.contributor.author","Tampe, Desiree"],["dc.contributor.author","Tampe, Björn"],["dc.contributor.author","Zeisberg, Michael"],["dc.date.accessioned","2022-01-11T14:06:04Z"],["dc.date.available","2022-01-11T14:06:04Z"],["dc.date.issued","2021"],["dc.description.abstract","Aryl hydrocarbon receptor nuclear translocator (ARNT) mediates anti-fibrotic activity in kidney and liver through induction of ALK3-receptor expression and subsequently increased Smad1/5/8 signaling. While expression of ARNT can be pharmacologically induced by sub-immunosuppressive doses of FK506 or by GPI1046, its anti-fibrotic activity is only realized when ARNT-ARNT homodimers form, as opposed to formation of ARNT-AHR or ARNT-HIF1α heterodimers. Mechanisms underlying ARNTs dimerization decision to specifically form ARNT–ARNT homodimers and possible cues to specifically induce ARNT homodimerization have been previously unknown. Here, we demonstrate that phosphorylation of the Ser77 residue is critical for ARNT–ARNT homodimer formation and stabilization. We further demonstrate that inhibition of PP2A phosphatase activity by LB100 enhances ARNT–ARNT homodimers both in vivo and in vitro (mouse tubular epithelial cells and human embryonic kidney cells). In murine models of kidney fibrosis, and also of liver fibrosis, combinations of FK506 or GPI1046 (to induce ARNT expression) with LB100 (to enhance ARNT homodimerization) elicit additive anti-fibrotic activities. Our study provides additional evidence for the anti-fibrotic activity of ARNT–ARNT homodimers and reveals Ser77 phosphorylation as a novel pharmacological target to realize the therapeutic potential of increased ARNT transactivation activity."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1038/s41598-021-03523-1"],["dc.identifier.pii","3523"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97817"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation.eissn","2045-2322"],["dc.title","PP2A phosphatase inhibition is anti-fibrotic through Ser77 phosphorylation-mediated ARNT/ARNT homodimer formation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","72"],["dc.bibliographiccitation.journal","Nephrology Dialysis Transplantation"],["dc.bibliographiccitation.lastpage","79"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Tampe, Bjoern"],["dc.contributor.author","Zeisberg, Michael"],["dc.date.accessioned","2018-11-07T09:35:45Z"],["dc.date.available","2018-11-07T09:35:45Z"],["dc.date.issued","2014"],["dc.description.abstract","Chronic kidney disease (CKD) which can lead to end-stage renal failure remains a principal challenge in Nephrology. While mechanistic studies provided extensive insights into the common pathways of fibrogenesis which underlie the progression of CKD, these pre-clinical studies fail to fully explain the vastly different progression slopes of individual patients. Recent studies provide evidence that genetic polymorphisms and epigenetic variations determine the individual susceptibility of patients to develop chronic progressive kidney disease. Here, we review recent insights that were provided by genome-wide association studies (GWASs), gene-linkage studies and epigenome analysis. The progression of CKD towards end-stage renal failure remains a principal unsolved problem in Nephrology as effective therapies and predictive tests are still not available [1, 2]. Chronic progressive kidney disease is caused by a wide range of diseases, with diabetes mellitus, hypertension and primary glomerulopathies being the most common causes in the Western world [3]. Infections, physical obstruction, interstitial nephritides and genetic cystic kidney diseases are also common causes of end-stage renal disease (ESRD) [3]. Regardless of the primary underlying disease, chronically injured kidneys are histomorphologically characterized by tubulointerstitial fibrosis [1]. In fact, the extent of tubulointerstitial fibrosis is the best predictor for kidney survival, irrespective of the underlying disease. For this reason, fibrosis is considered the common pathway of chronic progressive kidney disease [1]. Fibrogenesis is a pathological scarring process which involves accumulation of activated fibroblasts, excessive deposition of extracellular matrix, failed regeneration of tubular epithelium, microvascular rarefaction and (mostly sterile) inflammation [4]. Fibrogenesis depends on a complex interaction of the involved cell types which is orchestrated by an extensive network of growth factors and signalling pathways (which are reviewed extensively elsewhere) [1]. In view of the detailed mechanistic knowledge of the pathways that orchestrate renal fibrogenesis, it is puzzling why progression rates of CKD differ dramatically among patients with identical underlying diseases [1, 2]. The fibrotic pathways are known, but the switches that control their intensities and which determine the speed at which fibrosis moves along the progression slope are not yet understood [1, 2]. The concept that genetic polymorphisms are the basis for individual progression rates of CKD is an obvious and attractive one. Distinct susceptibilities of different mouse and rat strains to experimental CKD are a strong testament of the impact of genetic variations on renal fibrogenesis. Identification of the underlying genetic polymorphisms and mechanistic proof of their involvement in the progression of CKD, however, is an ongoing challenge. There are two basic approaches: one strategy is to perform unbiased screening to identify genes which are associated with chronic progressive kidney disease and to then prove their mechanistic relevance in experimental studies ('genotype to phenotype approach'). The second strategy is to selectively analyse polymorphisms of genes which have been identified in mechanistic studies as drivers of renal fibrogenesis with regard to their association with CKD (phenotype to genotype approach). The puzzling observation, however, is that genetic analysis and mechanistic studies so far rarely complement each other. The current state of affairs is reviewed in more detail below."],["dc.identifier.doi","10.1093/ndt/gft025"],["dc.identifier.isi","000342940300009"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32458"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1460-2385"],["dc.relation.issn","0931-0509"],["dc.title","Contribution of genetics and epigenetics to progression of kidney fibrosis"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]