Publications by authors named "Eric Neau"

Vascular calcification is an important risk factor for cardiovascular (CV) mortality in patients with chronic kidney disease (CKD). It is also a complex process involving osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) and abnormal deposition of minerals in the vascular wall. In an observational, multicenter European study, including 112 patients with CKD from Spain and 171 patients on dialysis from France, we used serum proteome analysis and further validation by ELISA to identify calprotectin, a circulating damage-associated molecular pattern protein, as being independently associated with CV outcome and mortality.

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Congenital anomalies of the kidney and the urinary tract (CAKUT) are the first cause of chronic kidney disease in childhood. Several genetic and environmental origins are associated with CAKUT, but most pathogenic pathways remain elusive. Considering the amniotic fluid (AF) composition as a proxy for fetal kidney development, we analyzed the AF proteome from non-severe CAKUT (n = 19), severe CAKUT (n = 14), and healthy control (n = 22) fetuses using LC-MS/MS.

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Congenital Anomalies of the Kidney and of the Urinary Tract (CAKUT) cover a broad range of disorders including abnormal kidney development caused by defective nephrogenesis. Here we explored the possible involvement of the low affinity p75 neurotrophin receptor (p75NTR) in CAKUT and nephrogenesis. In mouse, p75NTR was highly expressed in fetal kidney, located within cortical early nephrogenic bodies, and decreased rapidly after birth.

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While blocking the renin angiotensin aldosterone system (RAAS) has been the main therapeutic strategy to control diabetic kidney disease (DKD) for many years, 25-30% of diabetic patients still develop the disease. In the present work we adopted a systems biology strategy to analyze glomerular protein signatures to identify drugs with potential therapeutic properties in DKD acting through a RAAS-independent mechanism. Glomeruli were isolated from wild type and type 1 diabetic (Ins2Akita) mice treated or not with the angiotensin-converting enzyme inhibitor (ACEi) ramipril.

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Although a rare disease, bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage kidney disease in children. Ultrasound-based prenatal prediction of postnatal kidney survival in CAKUT pregnancies is far from accurate. To improve prediction, we conducted a prospective multicenter peptidome analysis of amniotic fluid spanning 140 evaluable fetuses with CAKUT.

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Background: Although renal fibrosis and inflammation have shown to be involved in the pathophysiology of obstructive nephropathies, molecular mechanisms underlying evolution of these processes remain undetermined. In an attempt towards improved understanding of obstructive nephropathy and improved translatability of the results to clinical practice we have developed a systems biology approach combining omics data of both human and mouse obstructive nephropathy.

Results: We have studied in parallel the urinary miRNome of infants with ureteropelvic junction obstruction and the kidney tissue miRNome and transcriptome of the corresponding neonatal partial unilateral ureteral obstruction (UUO) mouse model.

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Background: Renal tubulointerstitial fibrosis is the pathological hallmark of chronic kidney disease (CKD). Currently, inhibitors of the renin-angiotensin system (RAS) remain the sole therapy in human displaying antifibrotic properties. Further antifibrotic molecules are needed.

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miRNAs are short non-coding RNAs that control post-transcriptional regulation of gene expression. They are found ubiquitously in tissue and body fluids and participate in the pathogenesis of many diseases. Due to these characteristics and their stability, miRNAs could serve as biomarkers of different pathologies of the kidney.

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Severe inflammation characterizes rapidly progressive glomerulonephritides, and expression of the kinin B1 receptor (B1R) associates with inflammation. Delayed B1R blockade reduces renal inflammation in a model of unilateral ureteral obstruction, but whether B1R modulates the pathophysiology of glomerulonephritides is unknown. Here, we observed an association of B1R protein expression and inflammation, in both glomeruli and the renal interstitium, in biopsies of patients with glomerulonephritides, Henoch-Schönlein purpura nephropathy, and ANCA-associated vasculitis.

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We examined the capacity of delayed inhibition of plasminogen activator inhibitor-1 (PAI-1) to reduce tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO) in mice. Small peptides mimicking parts of urokinase (uPA) and tissular plasminogen activator (tPA) and serving as decoy molecules for PAI-1 were administered daily during the late stages (3 to 8 days) of UUO. Treatment with PAI-1 decoys reduced interstitial deposition of fibronectin, collagen III and collagen IV without changes in macrophage and myofibroblast infiltration.

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Acute renal inflammation represents a complex disease and its molecular basis remains incompletely defined. We examined changes of global renal gene expression in lipopolysacharide-treated wild-type and kinin B(1) receptor-knockout mice to better comprehend molecular mechanisms of acute renal inflammation and possible implications of the kinin B(1) receptor in early (inflammatory) stages of renal disease. Microarray data revealed that LPS-mediated renal inflammation is associated with strong induction of gene families that are mostly involved in inflammatory and immune response and cell adhesion, as well as genes associated with metabolism, signal transduction and transport.

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Tubulointerstitial fibrosis in chronic renal disease is strongly associated with progressive loss of renal function. We studied the potential involvement of lysophosphatidic acid (LPA), a growth factor-like phospholipid, and its receptors LPA(1-4) in the development of tubulointerstitial fibrosis (TIF). Renal fibrosis was induced in mice by unilateral ureteral obstruction (UUO) for up to 8 d, and kidney explants were prepared from the distal poles to measure LPA release into conditioned media.

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The kinin B2 receptor, which is constitutively expressed in a large number of tissues, mediates most of the known effects of bradykinin (BK). Normally undetectable in healthy tissues, the B1 receptor is strongly over-expressed under pathological conditions. BK is an important mediator in renal homeostasis and is mainly known for its natriuretic and vasodilatory effects.

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Article Synopsis
  • Unilateral ureteral obstruction (UUO) in mice models accelerated renal tubulointerstitial fibrosis, revealing that mice without the bradykinin B2-receptor were more prone to fibrosis.
  • ACE-inhibition was effective in reducing renal fibrosis induced by UUO, but the study found no significant difference in fibrosis levels between B2-receptor positive and negative mice, indicating that the B2-receptor may not play a role in ACE-inhibition's antifibrotic effects.
  • Overall, ACE-inhibitors outperformed AT1 receptor antagonists in mitigating fibrosis in both types of mice.
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Angiotensin-converting enzyme (ACE) inhibitors reduce the progression of various fibrotic renal diseases both in humans and in animal models. Unilateral ureteral obstruction (UUO) is an animal model of accelerated renal tubulointerstitial fibrosis that is attenuated by ACE inhibition. Although ACE inhibitors increase bradykinin concentrations in addition to their effect on angiotensin II formation, the role of bradykinin in renal fibrosis has not been studied.

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We investigated the effects of a 3-week treatment with various combinations of angiotensin-converting enzyme inhibitor (ACEI) and B1 and B2 bradykinin receptor (B1R and B2R) antagonists (B1A and B2A) and AT1 receptor antagonist on ERK 1 and 2 phosphorylation in isolated glomeruli from streptozotocin-treated diabetic rats (STZ rats). Body weight, glycemia, and blood pressure were monitored. The rats were divided into nine groups: (1) control; and groups 2-9 were STZ treated with (3) insulin, (4) ACEI, (5) ACEI + B1A, (6) ACEI + B2A, (7) B2A, (8) B1A, (9) AT1 antagonist.

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Background: The physiological effects of ACE inhibitors may act in part through a kinin-dependent mechanism. We investigated the effect of chronic ACE-inhibitor treatment on functional kinin B(1)- and B(2)-receptor expression, which are the molecular entities responsible for the biological effects of kinins.

Methods And Results: Rats were subjected to different 6-week treatments using various mixtures of the following agents: ACE inhibitor, angiotensin AT(1)-receptor antagonist, and B(1)- and B(2)-receptor antagonists.

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