A5021158640- Nitric Oxide and Endothelin Effects
- Cell Adhesion Molecules Research
- Chronic Kidney Disease and Diabetes
- Protein Tyrosine Phosphatases
- Renin-Angiotensin System Studies
- Ion Transport and Channel Regulation
- Bioactive Compounds and Antitumor Agents
- Renal and related cancers
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Hormonal Regulation and Hypertension
- Signaling Pathways in Disease
- Acute Kidney Injury Research
- Calpain Protease Function and Regulation
- Cancer, Hypoxia, and Metabolism
- Nanoparticle-Based Drug Delivery
- Receptor Mechanisms and Signaling
- Cardiac Fibrosis and Remodeling
- Galectins and Cancer Biology
- Advanced Glycation End Products research
- Eicosanoids and Hypertension Pharmacology
- Cardiac Ischemia and Reperfusion
- Adipokines, Inflammation, and Metabolic Diseases
- Dialysis and Renal Disease Management
- Adipose Tissue and Metabolism
- Graphene and Nanomaterials Applications
Fundación Renal
2018-2024
Instituto de Salud Carlos III
2012-2024
Universidad de Alcalá
2014-2024
Instituto Ramón y Cajal de Investigación Sanitaria
2018-2024
Graphenea (Spain)
2024
Madrid Health Service
2022-2023
Comunidad de Madrid
2014-2022
Hospital Universitario Príncipe de Asturias
2002-2016
Hospital Universitario Reina Sofía
2014
Universidad de Oviedo
2010
Many forms of vascular disease are characterized by increased transforming growth factor (TGF)-beta1 expression and endothelial dysfunction. Smad proteins a key step in TGF-beta-initiated signal transduction. We hypothesized that NO may regulate TGF-beta-dependent gene expression. show inhibits TGF-beta/Smad-regulated transactivation cGMP-dependent manner. effects were mimicked soluble analogue cGMP. Inhibition protein kinase 1 (PKG-1) or overexpression dominant-negative PKG-1alpha...
Integrin-linked kinase (ILK) is a key scaffolding protein between extracellular matrix and the cytoskeleton has been implicated previously in pathogenesis of renal damage. However, its involvement mitochondrial dysfunction remains to be elucidated. We studied role ILK downstream regulations damage mitochondria function both vivo vitro, using folic acid (FA)-induced kidney disease model. Wild type (WT) conditional-knockdown (cKD-ILK) mice were injected with single intraperitoneal dose FA...
In the last years, reactive oxygen species (ROS) have been proposed as mediators of proliferative/hypertrophic responses to angiotensin II (Ang II), both in vivo and vitro. However, hypothesis that Ang II-dependent cell contraction could be mediated by ROS, particularly H<sub>2</sub>O<sub>2</sub>, has not tested. Present experiments were devoted test this analyze possible mechanisms involved. Catalase (CAT) prevented increased myosin light chain phosphorylation decreased planar surface area...
Abstract Cardiovascular disease is an important cause of death in patients with chronic kidney (CKD). Protein-bound uremic toxins, such as p -cresyl and indoxyl sulfate (IS), are poorly removed during hemodialysis, leading to vascular endothelial dysfunction leukocyte extravasation. These processes can be related dynamic adhesion structures called podosomes. Several studies have indicated the role integrin-linked kinase (ILK) accumulation integrin-associated proteins Here, we investigated...
Abstract Background Traditional biomarkers of chronic kidney disease (CKD) detect the in its late stages and hardly predict associated vascular damage. Integrin-linked kinase (ILK) is a scaffolding protein serine/threonine that plays multiple roles several pathophysiological processes during renal However, involvement ILK as biomarker CKD problems remains to be fully elucidated. Methods was induced by an adenine-rich diet for 6 weeks mice. We used inducible knockdown mice (cKD-ILK) model...
We report the first examples of a new series antioxidant-sartan hybrids (AO-sartans), which were made by adding an antioxidant fragment to hydroxymethyl side chain losartan. Experiments performed in cultured cells demonstrate that these retain ability block angiotensin II effect with increased ability. In hypertensive rats, compounds show properties suggest they may be more useful than losartan for controlling hypertension and preventing hypertension-induced cardiovascular damage.
The development of insulin resistance is characterized by the impairment glucose uptake mediated transporter 4 (GLUT4). Extracellular matrix changes are induced when metabolic dysregulation sustained. present work was devoted to analyze possible link between extracellular-to-intracellular mediator integrin-linked kinase (ILK) and peripheral tissue modification that leads homeostasis impairment. Mice with general depletion ILK in adulthood (cKD-ILK) maintained a chow diet exhibited increased...
One of the clinical alterations observed in chronic renal disease (CRD) is impaired urine concentration, known as diabetes insipidus (DI). Tubulointerstitial fibrosis kidney also a pathological finding CRD and involves composition extracellular matrix (ECM). However, an association between these two events has not been elucidated. In this study, we showed that extracellular-to-intracellular scaffold protein integrin-linked kinase (ILK) regulates expression tubular water channel aquaporin-2...
Abstract Protein tyrosine phosphatase 1B (PTP1B) is a very promising target for the treatment of metabolic disorders such as type II diabetes mellitus. Although it was validated this disease more than 30 years ago, yet there no drug in advanced clinical trials, and its biochemical mechanism functions are still being studied. In present study, based on our experience generating PTP1B inhibitors, we have developed implemented scaffold‐hopping approach to vary pyrrole ring pyrrolo[1,2‐...
Hydrogen peroxide (H(2)O(2)) is an important mediator in the vasculature, but its role regulation of soluble guanylate cyclase (sGC) activity and expression not completely understood. The aim this study was to test effect H(2)O(2) on sGC function explore molecular mechanism involved.H(2)O(2) increased sGCβ1 protein steady-state levels rat aorta aortic smooth muscle cells (RASMCs) a time- dose-dependent manner, blocked by catalase. sGCα2 along with β1 subunit, whereas α1 subunit remained...
Objective: Since mesangial and endothelial cells interact in the kidney, present experiments were designed to analyze ability of human (HMC) modulate endothelin-1 (ET-1) synthesis by umbilical vein (HuVEC). Methods Results: The supernatants HuVEC/HMC contained significantly lower amounts ET-1 than those HuVEC alone. This effect was not due a decreased prepro-ET-1 mRNA expression only partially consequence HMC-dependent degradation. Therefore, we tested influence coculture on...
The aim of the present experiments was to evaluate differences in arterial pressure between H-Ras lacking mice and control analyze mechanisms involved genesis differences. mouse embryonic fibroblasts from these animals were used. Blood measured using 3 different methods: direct intraarterial measurement anesthetized animals, tail-cuff sphygmomanometer, radiotelemetry. showed lower blood than animals. Moreover, aorta protein content endothelial nitric oxide synthase, soluble guanylyl cyclase,...
Podosomes are integrin-based adhesions fundamental for stabilisation of the leading lamellae in migrating dendritic cells (DCs) and extracellular matrix (ECM) degradation. We have previously shown that soluble factors chemokines such as SDF 1-a trigger podosome initiation whereas integrin ligands promote maturation stability DCs. The exact intracellular signalling pathways regulate sequential organisation podosomal components response to cues remain largely undetermined. Wiskott Aldrich...
PTP1B dephosphorylates insulin receptor and substrates to modulate glucose metabolism. This enzyme is a validated therapeutic target for type 2 diabetes, but no current drug candidates have completed clinical trials. Pyrrolo[1,2-a]quinoxalines substituted at positions C1-C4 and/or C7-C8 were found be nontoxic cells good inhibitors in the low- sub-micromolar range, with 4-benzyl derivative being most potent inhibitor (0.24 μm). Some analogues bearing chlorine atoms C7 C8 kept potency showed...
Graphene-based GMC binds to integrinβ1/ILK cluster reduce adipocyte triglyceride storage in hypertrophied subcutaneous adipose tissue and increases, turn, ILK expression lipolysis.
Soluble guanylyl cyclase (sGC) is activated by nitric oxide (NO) and produces cGMP, which activates cGMP-dependent protein kinases (PKG) hydrolyzed specific phosphodiesterases (PDE). The vasodilatory cytoprotective capacity of cGMP-axis activation results in a therapeutic strategy for several pathologies. Integrin-linked kinase (ILK), major scaffold between the extracellular matrix intracellular signaling pathways, may modulate expression functionality cGMP-axis-related proteins. We...
Glomerular diseases are characterized by a sustained synthesis and accumulation of abnormal extracellular matrix proteins, such as collagen type I. The transmits information to cells through interactions with membrane components, which directly activate many intracellular signaling events. Moreover, accumulating evidence suggests that eicosanoids derived from cyclooxygenase (COX)-2 participate in number pathological processes immune-mediated renal diseases, it is known protein kinase B (AKT)...