The Experts below are selected from a list of 10398 Experts worldwide ranked by ideXlab platform

Bjorn Tampe - One of the best experts on this subject based on the ideXlab platform.

  • induction of tet3 dependent epigenetic remodeling by low dose hydralazine attenuates progression of chronic kidney disease
    EBioMedicine, 2015
    Co-Authors: Bjorn Tampe, Desiree Tampe, Elisabeth M Zeisberg, Gerhard A Muller, Wibke Bechtelwalz, Michael Koziolek, Raghu Kalluri
    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 that therapeutic use of low-dose Dihydralazine in patients with chronic kidney disease and fibrosis deserves further consideration.

Michele Buemi - One of the best experts on this subject based on the ideXlab platform.

  • neutrophil gelatinase associated lipocalin ngal as a marker of kidney damage
    American Journal of Kidney Diseases, 2008
    Co-Authors: Davide Bolignano, Valentina Donato, Giuseppe Coppolino, Susanna Campo, Antoine Buemi, Antonio Lacquaniti, Michele Buemi
    Abstract:

    Neutrophil gelatinase–associated lipocalin (NGAL) is a protein belonging to the lipocalin superfamily initially found in activated neutrophils, in accordance with its role as an innate antibacterial factor. However, it subsequently was shown that many other types of cells, including in the kidney tubule, may produce NGAL in response to various injuries. The increase in NGAL production and release from tubular cells after harmful stimuli of various kinds may have self-defensive intent based on the activation of specific iron-dependent pathways, which in all probability also represent the mechanism through which NGAL promotes kidney growth and differentiation. NGAL levels predict the future appearance of acute kidney injury after treatments potentially detrimental to the kidney and even the acute worsening of unstable nephropathies. Furthermore, recent evidence also suggests that NGAL somehow may be involved in the pathophysiological process of chronic renal diseases, such as polycystic kidney disease and glomerulonephritis. NGAL levels clearly correlate with severity of renal impairment, probably expressing the degree of active damage underlying the chronic condition. For all these reasons, NGAL may become one of the most promising next-generation biomarkers in Clinical Nephrology and beyond.

Raghu Kalluri - One of the best experts on this subject based on the ideXlab platform.

  • induction of tet3 dependent epigenetic remodeling by low dose hydralazine attenuates progression of chronic kidney disease
    EBioMedicine, 2015
    Co-Authors: Bjorn Tampe, Desiree Tampe, Elisabeth M Zeisberg, Gerhard A Muller, Wibke Bechtelwalz, Michael Koziolek, Raghu Kalluri
    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 that therapeutic use of low-dose Dihydralazine in patients with chronic kidney disease and fibrosis deserves further consideration.

Desiree Tampe - One of the best experts on this subject based on the ideXlab platform.

  • induction of tet3 dependent epigenetic remodeling by low dose hydralazine attenuates progression of chronic kidney disease
    EBioMedicine, 2015
    Co-Authors: Bjorn Tampe, Desiree Tampe, Elisabeth M Zeisberg, Gerhard A Muller, Wibke Bechtelwalz, Michael Koziolek, Raghu Kalluri
    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 that therapeutic use of low-dose Dihydralazine in patients with chronic kidney disease and fibrosis deserves further consideration.

Elisabeth M Zeisberg - One of the best experts on this subject based on the ideXlab platform.

  • induction of tet3 dependent epigenetic remodeling by low dose hydralazine attenuates progression of chronic kidney disease
    EBioMedicine, 2015
    Co-Authors: Bjorn Tampe, Desiree Tampe, Elisabeth M Zeisberg, Gerhard A Muller, Wibke Bechtelwalz, Michael Koziolek, Raghu Kalluri
    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 that therapeutic use of low-dose Dihydralazine in patients with chronic kidney disease and fibrosis deserves further consideration.