A5024912124- Chronic Kidney Disease and Diabetes
- Renal and related cancers
- Renal Diseases and Glomerulopathies
- Advanced Glycation End Products research
- Genetic and Kidney Cyst Diseases
- Biomedical Research and Pathophysiology
- Pancreatic function and diabetes
- Cell Adhesion Molecules Research
- Proteoglycans and glycosaminoglycans research
- Mitochondrial Function and Pathology
- Acute Kidney Injury Research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Birth, Development, and Health
- Renal Transplantation Outcomes and Treatments
- Heme Oxygenase-1 and Carbon Monoxide
- Glycosylation and Glycoproteins Research
- Renal cell carcinoma treatment
- Dialysis and Renal Disease Management
- Aldose Reductase and Taurine
- Renin-Angiotensin System Studies
- Connective tissue disorders research
- Adipose Tissue and Metabolism
- Genetic Syndromes and Imprinting
- T-cell and B-cell Immunology
- Endoplasmic Reticulum Stress and Disease
Northwestern University
2015-2024
Northwestern University
2023
Second Xiangya Hospital of Central South University
2023
Central South University
2023
Northwestern Memorial Hospital
2017-2022
RELX Group (United States)
2017-2020
Comprehensive Clinical Research
2015
Hypertension Institute
2015
Milbank Memorial Fund
2014
GTx (United States)
2010
There is a rapid global rise in obesity, and the link between obesity diabetes remains somewhat obscure. We identified an adipocytokine, designated as visceral adipose tissue-derived serpin (vaspin), which member of serine protease inhibitor family. Vaspin cDNA was isolated by from white tissues (WATs) Otsuka Long-Evans Tokushima fatty (OLETF) rat, animal model abdominal with type 2 diabetes. Rat, mouse, human vaspins are made up 392, 394, 395 amino acids, respectively; exhibit ≈40% homology...
Glomerular basement membranes (GBM's) were subjected to digestion in situ with glycosaminoglycan-degrading enzymes assess the effect of removing glycosaminoglycans (GAG) on permeability GBM native ferritin (NF). Kidneys digested by perfusion enzyme solutions followed NF. In controls treated buffer alone, NF was seen high concentration capillary lumina, but tracer did not penetrate any extent beyond lamina rara interna (LRI) GBM, and litte or no reached urinary spaces. Findings kidneys...
The glomerular basement membrane was subjected to digestion with specific enzymes determine the chemical nature (sialoglycoproteins, collagenous peptides, or glycosaminoglycans) of anionic sites previously demonstrated in laminae rarae. Enzyme carried out both situ and vitro . Kidneys were perfused enzyme solutions followed by perfusion fixative containing cationic dye, ruthenium red, detect sites. Glomerular membranes isolated detergent treatment glomeruli incubated solutions, incubation...
Cationized ferritin (CF) of narrow pI range (7.3-7.5) and the basic dye ruthenium red (RR) have been used as cationic probes to partially characterize anionic sites previously demonstrated in glomerular basement membrane (GBM). When CF was given i.v. normal rats left kidney fixed by perfusion 15 min thereafter, clusters molecules were found throughout lamina rara interna (LRI), externa (LRE), mesangial matrix distributed at regular (approximately 60 nm) intervals. kidneys perfused with...
NLRP3/IL-1β activation via thioredoxin (TRX)/thioredoxin-interacting protein (TXNIP) following mitochondria ROS (mtROS) overproduction plays a key role in inflammation. However, the involvement of this process tubular damage kidneys patients with diabetic nephropathy (DN) is unclear. Here, we demonstrated that mtROS accompanied by decreases TRX expression and TXNIP up-regulation. In addition, discovered also associated increases TGF-β DN db/db mice. We reversed these changes mice...
Diabetic kidney disease (DKD) is associated with oxidative stress and mitochondrial injury. Myo-inositol oxygenase (MIOX), a tubular-specific enzyme, modulates redox imbalance apoptosis in tubular cells diabetes, but these mechanisms remain unclear. We investigated the role of MIOX perturbation quality control, including dynamics autophagy/mitophagy, under high-glucose (HG) ambience or diabetic state. HK-2 LLC-PK1 subjected to HG exhibited an upregulation accompanied by fragmentation...
Overexpression of myo-inositol oxygenase (MIOX), a proximal tubular enzyme, exacerbates cellular redox injury in acute kidney (AKI). Ferroptosis, newly coined term associated with lipid hydroperoxidation, plays critical role the pathogenesis AKI. Whether or not MIOX damage by accelerating ferroptosis cisplatin-induced AKI remains elusive. Cisplatin-treated HK-2 cells exhibited notable cell death, which was reduced inhibitors. Also, alterations various metabolic sensors, including glutathione...
A 36-kDa β-galactoside mammalian lectin protein, designated as galectin-9, was isolated from mouse embryonic kidney by using a degenerate primer polymerase chain reaction and cloning strategy. Its deduced amino acid sequence had the characteristic conserved motif of galectins. Endogenous extracted liver thymus, well recombinant galectin-9 exhibited specific binding activity for lactosyl group. It two distinct N- C-terminal carbohydrate-binding domains connected link peptide, with no homology...
Galectin-9, a beta-galactoside binding lectin, has recently been isolated from murine embryonic kidney. In this study, its biological functions and expression in embryonic, newborn, adult mice tissues were investigated. By Northern blot analyses, it was found widely distributed developmentally regulated. situ hybridization studies revealed an accentuated of galectin-9 liver thymus mice. postnatal mice, antigalectin-9 immunoreactivity observed various tissues, including thymic epithelial...
Glycosaminoglycans were isolated from purified fractions of glomerular basement membranes and partially characterized by chemical analysis cellulose acetate electrophoresis. Basement prepared detergent treatment rat glomeruli subjected to digestion with papain Pronase. the digests precipitation cetyl pyridinium chloride ethanol. Results electrophoresis glycosaminoglycan fraction revealed presence one major minor spot. The spot was identified as heparan sulfate because it comigrated standard...
Klotho , an antiaging gene with restricted organ distribution, is mainly expressed in the kidney tubules; mutant mice have shortened life span, arteriosclerosis, anemia, and osteoporesis, features common to patients chronic renal failure. Conceivably, reduction of expression may contribute development failure; alternatively, its overexpression lead amelioration injury ICR-derived glomerulonephritis (ICGN) mouse model subtle immune complex-mediated disease. To address this issue, four...
Kidneys were perfused with [35S]sulfate at 4 h in vitro to radiolabel sulfated proteoglycans. Glomeruli isolated from the labeled kidneys, and purified fractions of glomerular basement membrane (GBM) prepared therefrom. Proteoglycans extracted GBM by use M guanidine-HCl degrees C presence protease inhibitors. The efficiency extraction was approximately 55% based on 35S radioactivity. proteoglycans characterized gel-filtration chromatography (before after degradative treatments) their...
Collectrin, a novel homolog of angiotensin-converting enzyme-related carboxypeptidase (ACE2), was identified during polymerase chain reaction-based cDNA subtraction and up-regulated in 5/6 ablated kidneys at hypertrophic phase. with 222 amino acids, has an apparent signal peptide transmembrane domain; the sequence is conserved mouse, rat, human shares 81.9% identity. Human collectrin 47.8% identity non-catalytic extracellular, transmembrane, cytosolic domains ACE2; however, unlike ACE ACE2,...
Inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, also known as statins, are lipid-lowering agents widely used in the prevention coronary heart disease. Recent experimental and clinical data, however, indicate that overall benefits statin therapy may exceed its cholesterol-lowering properties. We postulate statins ameliorate detrimental effects high glucose (HG)-induced proliferation mesangial cells (MCs), a feature early stages diabetic nephropathy, by preventing Rho...
Neph1-deficient mice develop nephrotic syndrome at birth, indicating the importance of this protein in development a normal glomerular filtration barrier. While precise subcellular localization Neph1 remains unknown, its relationship with other components barrier is great interest field. In paper, we localize expression to slit diaphragm by immunogold electron microscopy rodents and describe direct interaction two diaphragm, nephrin ZO-1. Both native recombinant associate each as dimers...
For investigation of how the vascular endothelial growth factor (VEGF) system participates in pathogenesis diabetic kidney disease, type 2 db/db and control db/m mice were treated intraperitoneally with vehicle or mg/kg a pan-VEGF receptor tyrosine kinase inhibitor, SU5416, twice week for 8 wk. Efficacy SU5416 treatment was verified by inhibition VEGF receptor-1 phosphorylation. Glomerular immunostaining, normally increased diabetes, unaffected SU5416. Plasma creatinine did not change...
Fibronectin (FN) has been localized in the rat glomerulus using indirect immunolabeling. It was demonstrated frozen sections by immunofluorescence, of fixed kidneys both peroxidase and ferritin-labeled antibodies, isolated glomerular basement membranes (GBM) with antibodies. Complementary convergent results were obtained these approaches. FN most abundant mesangial matrix where it especially concentrated at interface between endothelial cells. In peripheral capillary loop, also detected...