A5017058701- Renal and related cancers
- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Ion Transport and Channel Regulation
- Dialysis and Renal Disease Management
- Occupational exposure and asthma
- Renin-Angiotensin System Studies
- Occupational and environmental lung diseases
- Acute Kidney Injury Research
- Ultrasound and Hyperthermia Applications
- Genomics, phytochemicals, and oxidative stress
- Electrolyte and hormonal disorders
- Genetic and Kidney Cyst Diseases
- Iron Metabolism and Disorders
- Photoacoustic and Ultrasonic Imaging
- Tissue Engineering and Regenerative Medicine
- Liver Disease and Transplantation
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Birth, Development, and Health
- Blood Coagulation and Thrombosis Mechanisms
- Protease and Inhibitor Mechanisms
- Wnt/β-catenin signaling in development and cancer
- Hemoglobinopathies and Related Disorders
- Connective Tissue Growth Factor Research
University of Pittsburgh
2016-2025
United States Department of Veterans Affairs
2024
VA Pittsburgh Healthcare System
2024
Veterans Research Foundation of Pittsburgh
2023
Veterans Health Administration
2023
University of Pittsburgh Medical Center
2005-2020
Renal Association
2016
University of Washington
2005-2006
University of Helsinki
2005
VA Puget Sound Health Care System
2005
Aging is an independent risk factor for CKD, but the molecular mechanisms that link aging and CKD are not well understood. The antiaging protein Klotho may be endogenous antagonist of Wnt/β-catenin signaling, which promotes fibrogenesis, suggesting loss contribute to through increased activity. Here, normal adult kidneys highly expressed in tubular epithelium, various models nephropathy exhibited markedly less expression Klotho. Loss was closely associated with β-catenin diseased kidneys,...
AKI is increasingly recognized as a major risk factor for progression to CKD. However, the factors governing CKD are poorly understood. In this study, we investigated issue using moderate (20 minutes) and severe (30 ischemia/reperfusion injury (IRI) in mice. Moderate IRI led acute kidney failure transient Wnt/ β -catenin activation, which was followed by restoration of morphology function. resulted sustained exaggerated accompanied development renal fibrotic lesions characterized...
Activation of the renin-angiotensin system (RAS) plays an essential role in pathogenesis CKD and cardiovascular disease. However, current anti-RAS therapy only has limited efficacy, partly because compensatory upregulation renin expression. Therefore, a treatment strategy to simultaneously target multiple RAS genes is necessary achieve greater efficacy. By bioinformatics analyses, we discovered that promoter regions all contained putative T-cell factor (TCF)/lymphoid enhancer (LEF)-binding...
Matrix metalloproteinase-7 (MMP-7), a secreted zinc– and calcium–dependent endopeptidase, is transcriptional target of canonical Wnt/ β -catenin signaling. Because activated in diseased kidney, we hypothesized that urinary MMP-7 level may be used as noninvasive surrogate biomarker for fibrotic lesions. To test this hypothesis, conducted cross-sectional study, measuring levels cohort 102 patients with CKD. Compared normal subjects, various kidney disorders had markedly elevated MMP-7....
A variety of chronic kidney diseases exhibit reactivation Wnt/β-catenin signaling. In some tissues, β-catenin transcriptionally regulates matrix metalloproteinase-7 (MMP-7), but the association between MMP-7 and signaling in disease is unknown. Here, mouse models both obstructive nephropathy focal segmental glomerulosclerosis (adriamycin nephropathy), we observed upregulation mRNA protein a time-dependent manner. The pattern extent induction were positively associated with these models....
Tubular epithelium constitutes the majority of renal parenchyma and is primary target various kidney injuries. However, how injured tubules drive interstitial fibroblast activation proliferation remains poorly understood. Here, we investigated role sonic hedgehog (Shh), a secreted extracellular signaling protein, in proliferation. Shh was induced tubular epithelia animal models CKD by ischemia/reperfusion injury (IRI), adriamycin, or mass ablation, biopsy specimens from patients with...
Kidney fibrosis initiates at certain focal sites in which the fibrogenic niche provides a specialized microenvironment that facilitates fibroblast activation and proliferation. However, molecular identity of these niches is poorly characterized. Here, we determined whether tenascin-C (TNC), an extracellular matrix glycoprotein, component kidney fibrosis. In vivo, TNC expression increased rapidly kidneys subjected to unilateral ureteral obstruction or ischemia/reperfusion injury predominantly...
Abstract The role of NRF2 in kidney biology has received considerable interest over the past decade. transcriptionally controls genes responsible for cellular protection against oxidative and electrophilic stress anti‐inflammatory functions. is expressed throughout plays a salt water handling. In disease, animal studies show that protects tubulointerstitial damage reduces interstitial fibrosis tubular atrophy, may slow progression polycystic disease. However, proteinuric glomerular diseases...
Inhalation of asbestos fibers causes pulmonary inflammation and eventual fibrosis (asbestosis). Although the underlying molecular events are poorly understood, protease/antiprotease oxidant/antioxidant imbalances believed to contribute disease. Implicated in other forms fibrosis, matrix metalloproteinases (MMPs) have not been examined asbestosis. We therefore hypothesized that MMPs play a pathogenic role asbestosis development. Wild-type C57BL/6 mice were intratracheally instilled with 0.1...
With-no-lysine (WNK) kinases coordinate volume and potassium homeostasis by regulating renal tubular electrolyte transport. In the distal convoluted tubule (DCT), imbalance causes WNK signaling complexes to concentrate into large discrete foci, which we call “WNK bodies.” Although these structures have been reported previously, mechanisms that drive their assembly remain obscure. Here, show kidney-specific WNK1 (KS-WNK1), a truncated kinase-defective isoform is highly expressed in DCT,...
Renal denervation lowers arterial blood pressure (ABP) in multiple clinical trials and some experimental models of hypertension. These antihypertensive effects have been attributed to the removal renal afferent nerves. The purpose present study was define function, anatomy, contribution mouse sensory neurons a nerve-dependent model First, electrical stimulation nerves produced frequency-dependent increases ABP that were eliminated by ganglionic blockade. Stimulus-triggered averaging revealed...
Asbestosis is a form of interstitial lung disease caused by the inhalation asbestos fibers, leading to inflammation and pulmonary fibrosis. Inflammation oxidant/antioxidant imbalances are known contribute pathogenesis. Extracellular superoxide dismutase (EC-SOD) an antioxidant enzyme that has been shown protect from oxidant-mediated damage, inflammation, matrix (ECM) components, such as collagen glycosaminoglycans, be sensitive oxidative fragmentation. Heparan sulfate, glycosaminoglycan,...