Circulating soluble endoglin modifies the inflammatory response in mice.

Inflammation is associated with every health condition, and is an important component of many pathologies such as cardiovascular diseases. Circulating levels of soluble endoglin have been shown to be higher in the serum of patients with cardiovascular diseases with a significant inflammatory component. The aim of this study was to evaluate the implication of circulating soluble endoglin in the inflammatory response.

Mechanisms of triple whammy acute kidney injury.

Pre-renal acute kidney injury (AKI) results from glomerular haemodynamic alterations leading to reduced glomerular filtration rate (GFR) with no parenchymal compromise. Renin-angiotensin system inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor antagonists (ARAs), non-steroidal anti-inflammatory drugs (NSAIDs) and diuretics, are highly prescribed drugs that are frequently administered together. Double and triple associations have been correlated with increased pre-renal AKI incidence, termed "double whammy" and "triple whammy", respectively.

Activation of the ALK-5 Pathway is not per se Sufficient for the Antiproliferative Effect of TGF-β1 on Renal Tubule Epithelial Cells.

Background/aims: Defective tissue repair underlies renal tissue degeneration during chronic kidney disease (CKD) progression. Unbalanced presence of TGF-β opposes effective cell proliferation and differentiation processes, necessary to replace damaged epithelia. TGF-β also retains arrested cells in a fibrotic phenotype responsible for irreversible scarring.

Sub-nephrotoxic cisplatin sensitizes rats to acute renal failure and increases urinary excretion of fumarylacetoacetase.

Nephrotoxicity limits the therapeutic efficacy of the antineoplastic drug cisplatin. Due to dosage adjustment and appropriate monitoring, most therapeutic courses with cisplatin produce no or minimal kidney damage. However, we studied whether even sub-nephrotoxic dosage of cisplatin poses a potential risk for the kidneys by predisposing to acute kidney injury (AKI), specifically by lowering the toxicity threshold for a second nephrotoxin.

Interferon-γ Reduces the Proliferation of Primed Human Renal Tubular Cells.

Background/aims: Chronic kidney disease (CKD) is a progressive deterioration of the kidney function, which may eventually lead to renal failure and the need for dialysis or kidney transplant. Whether initiated in the glomeruli or the tubuli, CKD is characterized by progressive nephron loss, for which the process of tubular deletion is of key importance. Tubular deletion results from tubular epithelial cell death and defective repair, leading to scarring of the renal parenchyma.

Met signaling in cardiomyocytes is required for normal cardiac function in adult mice.

Hepatocyte growth factor (HGF) and its receptor, Met, are key determinants of distinct developmental processes. Although HGF exerts cardio-protective effects in a number of cardiac pathologies, it remains unknown whether HGF/Met signaling is essential for myocardial development and/or physiological function in adulthood. We therefore investigated the requirement of HGF/Met signaling in cardiomyocyte for embryonic and postnatal heart development and function by conditional inactivation of the Met receptor in cardiomyocytes using the Cre-α-MHC mouse line (referred to as α-MHCMet-KO).

Alteration in endoglin-related angiogenesis in refractory cytopenia with multilineage dysplasia.

The functional mechanisms involved in angiogenesis and the potential role of endoglin (ENG), recently described as a new marker for this process, have not been explored in Myelodysplastic Syndromes (MDS). In order to gain insight in MDS angiogenesis a combined analysis in bone marrow (BM) of gene expression levels, angiogenesis-related soluble factors and functional angiogenesis-related studies was carried out. Ninety-seven MDS patients and forty-two normal BM samples were studied.

Increased urinary excretion of albumin, hemopexin, transferrin and VDBP correlates with chronic sensitization to gentamicin nephrotoxicity in rats.

Drug nephrotoxicity is a serious health and economic problem worldwide. Rats can be acutely sensitized to acute kidney injury (AKI) by subnephrotoxic treatments with potentially nephrotoxic drugs. Acquired sensitization to AKI poses a silent risk impossible to diagnose pre-emptively with the technology available at the clinical level.

The role of the TGF-β coreceptor endoglin in cancer.

Endoglin (CD105) is an auxiliary membrane receptor of transforming growth factor beta (TGF-β) that interacts with type I and type II TGF-β receptors and modulates TGF-β signaling. Endoglin is overexpressed in the tumor-associated vascular endothelium, where it modulates angiogenesis. This feature makes endoglin a promising target for antiangiogenic cancer therapy.

Targeted genomic disruption of h-ras induces hypotension through a NO-cGMP-PKG pathway-dependent mechanism.

The aim of the present experiments was to evaluate the differences in arterial pressure between H-Ras lacking mice and control mice and to analyze the mechanisms involved in the genesis of the differences. H-Ras lacking mice and mouse embryonic fibroblasts from these animals were used. Blood pressure was measured using 3 different methods: direct intraarterial measurement in anesthetized animals, tail-cuff sphygmomanometer, and radiotelemetry.

Nephrotoxicity of uranium: pathophysiological, diagnostic and therapeutic perspectives.

As in the case of other heavy metals, a considerable body of evidence suggests that overexposure to uranium may cause pathological alterations to the kidneys in both humans and animals. In the present work, our aim was to analyze the available data from a critical perspective that should provide a view of the real danger of the nephrotoxicity of this metal for human beings. A further aim was to elaborate a comparative compilation of the renal pathophysiological data obtained in humans and experimental animals with a view to gaining more insight into our knowledge of the mechanisms of action and renal damage.

Differential effects of 17beta-estradiol and raloxifene on bone and lipid metabolism in rats with chronic kidney disease and estrogen insufficiency.

Objective: The aim of this study was to evaluate the effect of 17beta-estradiol, raloxifene, and 1-alpha,25-dihydroxycholecalciferol or calcitriol on bone and lipid metabolism in chronic kidney disease and estrogen insufficiency.

Methods: Six-month-old female Sprague-Dawley rats (n = 48) were ovariectomized and nephrectomized (seven eighths). One week after surgery, the rats were divided into six groups and treated with (1) placebo, (2) 17beta-estradiol 10 microg kg day, (3) raloxifene 1 mg kg day, (4) calcitriol 10 ng kg day, (5) 17beta-estradiol + calcitriol, and (6) raloxifene + calcitriol.

Lanthanum activates calcium-sensing receptor and enhances sensitivity to calcium.

Background: The aim of this study was to investigate whether nanomolar concentrations of lanthanum could influence the calcium-sensing receptor (CaSR) response.

Methods: Embryonic kidney (HEK-293) cells transiently transfected with the human CaSR were used to test the ability of lanthanum to activate the CaSR, either alone or in combination with calcium. CaSR activation was measured by flow cytometry.

Inflammation and EMT: an alliance towards organ fibrosis and cancer progression.

Recent advances in our understanding of the molecular pathways that govern the association of inflammation with organ fibrosis and cancer point to the epithelial to mesenchymal transition (EMT) as the common link in the progression of these devastating diseases. The EMT is a crucial process in the development of different tissues in the embryo and its reactivation in the adult may be regarded as a physiological attempt to control inflammatory responses and to 'heal' damaged tissue. However, in pathological contexts such as in tumours or during the development of organ fibrosis, this healing response adopts a sinister nature, steering these diseases towards metastasis and organ failure.

Prospective comparative analysis of the angiogenic capacity of monocytes and CD133+ cells in a murine model of hind limb ischemia.

Background Aims: The aim of this study was to compare prospectively the vasculogenic capacity of two cell sources, monocytes and CD133+ cells.

Methods: Cells were obtained from healthy donors by adherence or magnetic selection. Animals studies were performed in a model of hind limb ischemia and different groups were established according to type and number of cells infused.

Endoglin as a marker in cervical paragangliomas.

Background: Endoglin is expressed on endothelium and is implicated in the control of angiogenesis. This study compares the expression of endoglin with vascular endothelial growth factor (VEGF), commonly used as a marker for neoangiogenesis in cervical paragangliomas (CPG).

Methods: The CPG were surgically obtained from 5 patients and compared with nontumoral lung obtained from patients subjected to pulmonary resection.

Beneficial effects of vasodilators in preventing severe acute pancreatitis shock.

Objectives: To investigate the effect of treatment with several vasodilatory substance on the changes in mean arterial pressure (MAP) of severe acute pancreatitis.

Methods: Pancreatitis was induced in rats by 5% sodium taurocholate retrograde infusion through the pancreatic duct, which produces a significant decrease in arterial blood pressure.

Results: Three hours after the induction of pancreatitis, a fall of approximately 25 mm Hg in MAP was observed, with no changes of MAP in untreated controls.

Relationships between NOS2 and HO-1 in liver of rats with chronic bile duct ligation.

An increased expression and activity of the heme oxygenase-1 (HO-1) in the liver has been observed in models of hepatic damage. Nitric oxide (NO) seems to be involved in HO-1 regulation. The aim of this work is to assess HO-1 induction and heme oxygenase (HO) activity in rats with bile duct ligation (BDL).

Characterization of murine S-endoglin isoform and its effects on tumor development.

Endoglin is a transmembrane glycoprotein that acts as an auxiliary receptor for transforming growth factor-beta (TGF-beta) and modulates cellular responses to this pleiotropic cytokine. Endoglin is strongly expressed in endothelial cells, where it appears to exert a crucial role in vascular development and angiogenesis. Two endoglin isoforms (L and S), differing in their cytoplasmic domains, have been previously characterized in human tissues.

Matrix metalloproteinase 13 mediates nitric oxide activation of endothelial cell migration.

To explore the mechanisms by which NO elicits endothelial cell (EC) migration we used murine and bovine aortic ECs in an in vitro wound-healing model. We found that exogenous or endogenous NO stimulated EC migration. Moreover, migration was significantly delayed in ECs derived from endothelial NO synthase-deficient mice compared with WT murine aortic EC.

Role of vascular nitric oxide in experimental liver cirrhosis.

One of the most important features of liver cirrhosis is the splanchnic and systemic arterial vasodilation, related to an increase in vascular capacity and an active vasodilation. This arterial vasodilation seems to be the consequence of the excessive generation of vasodilating substances, which also contributes to a lower than normal pressor response to circulating nervous or humoral substances. The following review analyzes the mechanisms responsible for the vascular hyporesponse to vasoconstrictors observed in the experimental models of liver cirrhosis.

Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic acute renal failure.

Background: The relative roles of endothelin (ET)-1 and angiotensin (ANG) II in post-ischaemic acute renal failure (ARF) have not been fully established so far. With the aim of contributing to this goal, we assessed in this study the effect of ANG II and ET-1 blockade on the course of post-ischaemic-ARF.

Methods: Anaesthetized Wistar rats received i.

Expression of the TGF-beta coreceptor endoglin in epidermal keratinocytes and its dual role in multistage mouse skin carcinogenesis.

Endoglin is an integral membrane glycoprotein primarily expressed in the vascular endothelium, but also found on macrophages and stromal cells. It binds several members of the transforming growth factor (TGF)-beta family of growth factors and modulates TGF-beta(1)-dependent cellular responses. However, it lacks cytoplasmic signaling motifs and is considered as an auxiliary receptor for TGF-beta.

In vivo bradykinin B2 receptor activation reduces renal fibrosis.

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.

Expression of endoglin in human mesangial cells: modulation of extracellular matrix synthesis.

Transforming growth factor-beta (TGF-beta) has been identified as a key mediator of glomerulosclerosis in kidney diseases. Endoglin is a component of the TGF-beta receptor system that is upregulated during glomerulosclerosis, suggesting a role during progression of renal diseases characterized by extracellular matrix (ECM) synthesis and accumulation. The expression of endoglin was demonstrated in cultured human mesangial cells (HMC) by flow cytometry, Northern blot, reverse transcriptase polymerase chain reaction (RT-PCR), and Western blot analyses.