Endothelin-1 and Endothelin A Receptor Immunoreactivity Is Increased in Patients with Diabetic Nephropathy

Zanatta, Claudete Maria; Veronese, Francisco Veríssimo; Loreto, Melina Silva de; Sortica, Denise Alves; Carpio, Virna Nowotny; Eldeweiss, Maria Isabel Albano; Silva, Vinícius Duval da; Lopes, Tiago Giuglianni; Gross, Jorge Luiz; Canani, Luís Henrique Santos

doi:10.3109/0886022x.2011.647301

Cited by 32 publications

(21 citation statements)

References 28 publications

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“…It participates in podocyte dysfunction, inflammation and fibrosis and promotes mesangial cell proliferation and sclerosis. Increased staining for EDN1 in endothelial cells of glomerular and peritubular capillaries was observed in patients with diabetic nephropathy and IgAN compared with controls (Zanatta et al 2012). In our study, using the GeneGO Metacore software the possible involvement of NF-κB signaling in glomerular injury in patients with IgAN progression was proposed.…”

Section: Discussionmentioning

confidence: 59%

Molecular Profiling in IgA Nephropathy and Focal and Segmental Glomerulosclerosis

Tycova¹,

Hrubá

Maixnerová³

et al. 2018

Physiol Res

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The aim of the study was to characterize by molecular profiling two glomerular diseases: IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) and to identify potential molecular markers of IgAN and FSGS progression. The expressions of 90 immune-related genes were compared in biopsies of patients with IgAN (n=33), FSGS (n=17) and in controls (n=11) using RT-qPCR. To identify markers of disease progression, gene expression was compared between progressors and non-progressors in 1 year follow-up. The results were verified on validation cohort of patients with IgAN (n=8) and in controls (n=6) using laser-capture microdissection, that enables to analyze gene expression separately for glomeruli and interstitium. In comparison to controls, patients with both IgAN and FSGS, had lower expression of BAX (apoptotic molecule BCL2-associated protein) and HMOX-1 (heme oxygenase 1) and higher expression of SELP (selectin P). Furthermore, in IgAN higher expression of PTPRC (protein-tyrosine phosphatase, receptor-type C) and in FSGS higher expression of BCL2L1 (regulator of apoptosis BCL2-like 1) and IL18 compared to control was observed. Validation of differentially expressed genes between IgAN and controls on another cohort using laser-capture microdissection confirmed higher expression of PTPRC in glomeruli of patients with IgAN. The risk of progression in IgAN was associated with higher expression EDN1 (endothelin 1) (AUC=0.77) and FASLG (Fas ligand) (AUC=0.82) and lower expression of VEGF (vascular endothelial growth factor) (AUC=0.8) and in FSGS with lower expression of CCL19 (chemokine (C-C motif) ligand 19) (AUC=0.86). Higher expression of EDN1 and FASLG along with lower expression of VEGF in IgAN and lower expression of CCL19 in FSGS at the time of biopsy can help to identify patients at risk of future disease progression.

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Section: Discussionmentioning

confidence: 59%

Molecular Profiling in IgA Nephropathy and Focal and Segmental Glomerulosclerosis

Tycova¹,

Hrubá

Maixnerová³

et al. 2018

Physiol Res

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“…Immunohistochemistry was chosen to detect ET‐1 in the laminar tissue, because it was shown that endothelial cells secrete 80% of ET‐1 abluminally in the direction of the tunica media . This method has successfully been used in kidney tissue of human patients with type 2 diabetes, where its higher expression compared with healthy control subjects was proved . One study on ET‐1 expression has used plasma concentration to monitor ET‐1 in clinically endotoxaemic horses ; however, this was not feasible in the present study owing to the need for repeated reservoir exchanges.…”

Section: Discussionmentioning

confidence: 99%

Hyperinsulinaemia increases vascular resistance and endothelin‐1 expression in the equine digit

Gauff

Patan-Zugaj

Licka

2013

Equine Veterinary Journal

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SummaryReasons for performing study: Insulin leads to overexpression of endothelin-1 (ET-1) in the endothelium of insulin-resistant rodents. If this is also the case in equine laminar tissue, this could explain the predisposition of insulin-resistant horses to laminitis. Objectives: To investigate the effect of hyperinsulinaemia on metabolism and vascular resistance of the isolated equine digit in a model of extracorporeal perfusion. Study design: Randomised, controlled study with interventional group, with blinded evaluation of histology results. Method: After exsanguination, equine digits (n = 11) and autologous blood were collected at an abattoir. One digit served as a hyperinsulinaemic pilot limb, 5 digits were assigned to the hyperinsulinaemic perfusion (IP) group and 5 to the control perfusion (CP) group. Digits were perfused for 10 h at a defined perfusion rate of 12 ml/min/kg. After the first hour of perfusion (equilibration period), insulin was added to the reservoir of the IP digits. Perfusion pressure, glucose consumption, lactate and lactate dehydrogenase were monitored. Vascular resistance was calculated as perfusion pressure (in millimetres of mercury) in relation to the flow rate (in millilitres per minute). After perfusion, histology samples of the dorsal hoof wall (haematoxylin & eosin or periodic acid-Schiff) were evaluated. Immunohistology with a polyclonal rabbit-derived anti-endothelin antibody was used for detection of ET-1. Results: In the IP group, the mean insulin concentration in the plasma of the perfusate was 142 Ϯ 81 miu/ml, while insulin concentration was <3 miu/ml in the CP group. Mean vascular resistance was significantly higher (P<0.01) in the IP group (2.04 Ϯ 1.13 mmHg/ml/min) than in the CP group (1.31 Ϯ 0.55 mmHg/ml/min). Histology of the IP group samples showed significantly more vessels with an open lumen, increased width of the secondary epidermal lamellae and formation of oedema. In the lamellar vessels (veins and arteries) and nerve fibres, ET-1 expression was much more prominent in the IP group than in the CP group samples. Conclusions: Short-term hyperinsulinaemia leads to increased vascular resistance in the equine digit and increased expression of ET-1 in the laminar tissue.

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“…10,11 Hyperglycemia and impaired metabolic control may enhance vascular production of ET-1 in diabetes, which leads to glomerular damage by increasing vasoconstriction, mesangial cell proliferation and glomerular permeability. 12 Increased plasma concentration of ET-1 in patients with diabetes has been reported, 13,14 and a significant correlation has also been observed between plasma ET-1 levels and diabetic complications 15,16 but the relationship between ET-1 and indices of renal function is conflictive. It is known that patients with advanced chronic kidney disease or on dialysis have higher plasma concentrations of ET-1.…”

Section: Introductionmentioning

confidence: 99%

Plasma endothelin-1 level, measured glomerular filtration rate and effective renal plasma flow in diabetic nephropathy

et al. 2015

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Background: Endothelin-1 (ET-1) is potent vasoconstrictor peptide which is able to contribute to the functional and structural renal changes. The aim of this study was to investigate the relationship between plasma concentration of ET-1 and indices of renal function in patients with diabetic nephropathy. Methods: We measured plasma ET-1 levels in 99 patients with type 2 diabetes, divided into two groups according to the values of their glomerular filtration rate (GFR): group I (GFR ! 60 mL/min/1.73 m

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Endothelin-1 and Endothelin A Receptor Immunoreactivity Is Increased in Patients with Diabetic Nephropathy

Abstract: In this preliminary report, the higher expressions of ET-1 and ET-RA found in both DN and IgA nephropathy suggest a potential role for the endothelin system in DN as well as in other nondiabetic glomerular diseases.

Cited by 32 publications

References 28 publications

Molecular Profiling in IgA Nephropathy and Focal and Segmental Glomerulosclerosis

Molecular Profiling in IgA Nephropathy and Focal and Segmental Glomerulosclerosis

Hyperinsulinaemia increases vascular resistance and endothelin‐1 expression in the equine digit

Plasma endothelin-1 level, measured glomerular filtration rate and effective renal plasma flow in diabetic nephropathy

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