A5042782798- Chronic Kidney Disease and Diabetes
- Inflammatory mediators and NSAID effects
- Eicosanoids and Hypertension Pharmacology
- Renin-Angiotensin System Studies
- Hormonal Regulation and Hypertension
- Renal Diseases and Glomerulopathies
- Acute Kidney Injury Research
- Ion Transport and Channel Regulation
- Renal and related cancers
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Pharmacogenetics and Drug Metabolism
- Nitric Oxide and Endothelin Effects
- MRI in cancer diagnosis
- Cell Adhesion Molecules Research
- Diabetes Treatment and Management
- Cancer-related gene regulation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Organ Donation and Transplantation
- Advanced Glycation End Products research
- Genetic and Kidney Cyst Diseases
- Pediatric Urology and Nephrology Studies
- Electrolyte and hormonal disorders
- Liver physiology and pathology
- Advanced MRI Techniques and Applications
Vanderbilt University Medical Center
2016-2025
Vanderbilt University
2015-2024
VA Tennessee Valley Healthcare System
2012-2024
Hypertension Institute
2006-2024
United States Department of Veterans Affairs
1988-2024
Institute of Molecular Biology and Biophysics
2010-2024
RELX Group (United States)
2023
Providence Health Care
2022
Toronto General Hospital
2022
Vanderbilt Health
2018-2021
Gene targeting was used to create a null allele at the epidermal growth factor receptor locus ( Egfr ). The phenotype dependent on genetic background. EGFR deficiency CF-1 background resulted in peri-implantation death due degeneration of inner cell mass. On 129/Sv background, homozygous mutants died mid-gestation placental defects; CD-1 lived for up 3 weeks and showed abnormalities skin, kidney, brain, liver, gastrointestinal tract. multiple associated with indicate that is involved wide...
ABSTRACT. Hyperuricemia is associated with renal disease, but it usually considered a marker of dysfunction rather than risk factor for progression. Recent studies have reported that mild hyperuricemia in normal rats induced by the uricase inhibitor, oxonic acid (OA), results hypertension, intrarenal vascular and injury. This led to hypothesis uric may contribute progressive disease. To examine effect on disease progression, were fed 2% OA 6 wk after 5/6 remnant kidney (RK) surgery or...
The kidney is a rich source of prostaglandins. These eicosanoids, formed by cyclooxygenase-dependent metabolism arachidonic acid, are important physiologic mediators renal glomerular hemodynamics and tubular sodium water reabsorption. Two separate isoforms cyclooxygenase (COX) have now been identified: constitutive COX-1, encoded 2.8-kb mRNA, mitogen-activated COX-2, 4.0-4.5-kb mRNA. COX-2 expression increases during development inflammation, but, except for brain, low. It has generally...
The demonstration of in vivo arachidonic acid epoxidation and ω-hydroxylation established the cytochrome P450 epoxygenase ω/ω–1 hydroxylase as formal metabolic pathways members arachidonate cascade. characterization potent biological activities associated with several P450-derived eicosanoids suggested new important functional roles for these enzymes cellular, organ, body physiology, including control vascular reactivity systemic blood pressures. Past current advances biochemistry molecular...
We investigated the actions of endothelin in anesthetized rats and cultured mesangial cells. Intravenous infusion (10 pmol/min) decreased renal blood flow by 44% at 20 min without changing arterial pressure, which subsequently rose significantly from 124 +/- 3 to 133 4 mmHg over 60 min. Micropuncture during nonhypertensive period revealed increases afferent (65%) efferent (82%) arteriolar resistances, thereby reducing nephron plasma rate. The glomerular ultrafiltration coefficient (Kf) fell...
Functionally significant polymorphisms in endothelial nitric oxide synthase (eNOS) and reduced vascular eNOS activity have been associated with increased human diabetic nephropathy (DN), but the pathogenic role of deficiency development DN has not yet confirmed. This study characterizes severity eNOS(-/-) mice that were backcrossed to C57BLKS/J db/db mice. Although hyperglycemia was similar mice, by 26 wk, exhibited dramatic albuminuria, arteriolar hyalinosis, glomerular basement membrane...
Transformative technologies are enabling the construction of three dimensional (3D) maps tissues with unprecedented spatial and molecular resolution. Over next seven years, NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping human body at single-cell resolution by supporting technology development, data acquisition, detailed mapping. HuBMAP will integrate its efforts other funding agencies, programs,...
Renal tubule epithelia represent the primary site of damage in acute kidney injury (AKI), a process initiated and propagated by infiltration macrophages. Here we investigated role resident renal macrophages dendritic cells recovery from AKI after ischemia/reperfusion (I/R) or novel diphtheria toxin–induced (DT-induced) model selective proximal mice. DT-induced was characterized marked tubular cell apoptosis. In both models, macrophage/dendritic depletion during phase increased functional...
Sirtuin 1 (Sirt1) is a NAD+-dependent deacetylase that exerts many of the pleiotropic effects oxidative metabolism. Due to local hypoxia and hypertonicity, renal medulla subject extreme stress. Here, we set out investigate role Sirt1 in kidney. Our initial analysis indicated it was abundantly expressed mouse medullary interstitial cells vivo. Knocking down expression primary substantially reduced cellular resistance stress, while pharmacologic activation using either resveratrol or SRT2183...
The mechanisms by which angiotensin II (Ang II) promotes renal fibrosis remain incompletely understood. Ang both stimulates TGFβ signaling and activates the EGF receptor (EGFR), but relative contribution of these pathways to fibrogenesis is unknown. Using a murine model with EGFR-deficient proximal tubules, we demonstrate that upstream activation EGFR-dependent ERK critical for mediating sustained expression in fibrosis. Persistent stimulated ROS-dependent phosphorylation Src, leading...
The epidermal growth factor receptor (EGFR) is the prototypical member of a family membrane-associated intrinsic tyrosine kinase receptors, ErbB family. EGFR activated by multiple ligands, including EGF, transforming (TGF)-α, HB-EGF, betacellulin, amphiregulin, epiregulin, and epigen. expressed in organs plays important roles proliferation, survival, differentiation both development normal physiology, as well pathophysiological conditions. In addition, transactivation underlies some biologic...
Natriuretic regulation of extracellular fluid volume homeostasis includes suppression the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed control Here, we have demonstrated concentration, therefore conservation, an important system for formation in mice humans across various levels salt intake....
Abstract Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this are largely unknown. Clonal hematopoiesis of indeterminate potential (CHIP) confers increased several chronic diseases associated with aging. Here we sought to test whether CHIP increases AKI. In three population-based epidemiology cohorts, found that was greater incident AKI, which more pronounced in patients AKI requiring dialysis and individuals somatic mutations genes...
Two nonradioactive methods for determining glomerular filtration rate (GFR) in conscious mice using FITC-labeled inulin (FITC-inulin) were evaluated. The first method measured GFR clearance kinetics of plasma FITC-inulin after a single bolus injection. Based on two-compartment model, estimated was 236.69 ± 16.55 and 140.20 22.27 μl/min male female C57BL/6J mice, respectively. Total or ⅚ nephrectomy reduced to 0 32.80 9.32 μl/min, Conversely, diabetes mellitus induced by streptozotocin...
Atherosclerosis has features of an inflammatory disease. Because cyclooxygenase (COX)-2 is expressed in atherosclerotic lesions and promotes inflammation, we tested the hypotheses that selective COX-2 inhibition would reduce early lesion formation LDL receptor-deficient (LDLR-/-) mice macrophage expression contributes to atherogenesis LDLR-/- mice.Treatment male fed Western diet with rofecoxib or indomethacin for 6 weeks resulted significant reductions atherosclerosis proximal aorta (25%...