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Reduced O-GlcNAcylation and tubular hypoxia contribute to the antifibrotic effect of SGLT2 inhibitor dapagliflozin in the diabetic kidney.

April 1, 2020

Am J Physiol Renal Physiol

Abstract Diabetic kidney disease is a worldwide epidemic, and therapies are incomplete. Clinical data suggest that improved renal outcomes by Na-glucose cotransporter 2 inhibitor (SGLT2i) are partly beyond their antihyperglycemic effects; however, the mechanisms are still elusive. Here, we investigated the effect of the SGLT2i dapagliflozin (DAPA) in the prevention of elevated -GlcNAcylation and tubular […]

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A non-invasive biomarker of type III collagen degradation reflects ischaemia reperfusion injury in rats.

August 1, 2019

Nephrol Dial Transplant

Abstract BACKGROUND Maintenance of kidney function in kidney allografts remains a challenge, as the allograft often progressively develops fibrosis after kidney transplantation. Fibrosis is caused by the accumulation of extracellular matrix proteins like type I and III collagen (COL I and III) that replace the functional tissue. We assessed the concentrations of a neo-epitope fragment […]

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RAAS inhibitors directly reduce diabetes-induced renal fibrosis via growth factor inhibition.

January 1, 2019

J Physiol

Abstract KEY POINTS Increased activation of the renin-angiotensin-aldosterone system (RAAS) and elevated growth factor production are of crucial importance in the development of renal fibrosis leading to diabetic kidney disease. The aim of this study was to provide evidence for the antifibrotic potential of RAAS inhibitor (RAASi) treatment and to explore the exact mechanism of […]

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Urinary collagen degradation products as early markers of progressive renal fibrosis.

March 20, 2017

J Transl Med

Abstract BACKGROUND Renal fibrogenesis is associated with increased ECM remodeling and release of collagen fragments in urine in progressive renal disease. We investigated the diagnostic value of urinary collagen degradation products in a proteinuria-driven fibrosis rat model with and without anti-fibrotic S1P-receptor modulator FTY720 treatment. METHODS Proteinuria was induced in male Wistar rats by Adriamycin […]

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Protein fingerprinting of the extracellular matrix remodelling in a rat model of liver fibrosis–a serological evaluation.

March 1, 2013

Liver Int

Abstract BACKGROUND/AIM We investigated nine novel biomarkers of extracellular matrix (ECM) remodelling in a rat model of liver fibrosis. METHODS Liver fibrosis was induced in 52 male Wistar rats by inhalation of carbon tetrachloride and the level of hepatic fibrosis was assessed by Sirius red staining compared with controls. The novel serum biochemical markers assessed […]

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A novel marker for assessment of liver matrix remodeling: an enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M).

November 1, 2011

Biomarkers

Abstract A competitive enzyme-linked immunosorbent assay (ELISA) for detection of a type I collagen fragment generated by matrix metalloproteinases (MMP) -2, -9 and -13, was developed (CO1-764 or C1M). The biomarker was evaluated in two preclinical rat models of liver fibrosis: bile duct ligation (BDL) and carbon tetra chloride (CCL4)-treated rats. The assay was further […]

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Immunological detection of the type V collagen propeptide fragment, PVCP-1230, in connective tissue remodeling associated with liver fibrosis.

August 1, 2011

Biomarkers

Abstract AIM Liver fibrosis involves excessive remodeling and deposition of fibrillar extracellular matrix (ECM) components, which leads to malfunction of the organ, causing significant morbidity and mortality. The aim of this study was to assess whether levels of a type V collagen fragment, the propeptide CO5-1230, indicate the amount of collagen deposited during liver fibrosis. […]

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MMP mediated degradation of type VI collagen is highly associated with liver fibrosis–identification and validation of a novel biochemical marker assay.

January 1, 2011

PLoS One

Abstract BACKGROUND AND AIMS During fibrogenesis, in which excessive remodeling of the extracellular matrix occurs, both the quantity of type VI collagen and levels of matrix metalloproteinases, including MMP-2 and MMP-9, increase significantly. Proteolytic degradation of type VI collagen into small fragments, so-called neo-epitopes, may be specific biochemical marker of liver fibrosis. The aim of […]

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