Learn More
Thiazolidinediones (TZDs) are widely used to treat type 2 diabetes mellitus; however, their use is complicated by systemic fluid retention. Along the nephron, the pharmacological target of TZDs, peroxisome proliferator-activated receptor-gamma (PPARgamma, encoded by Pparg), is most abundant in the collecting duct. Here we show that mice treated with TZDs(More)
Increased plasminogen activator inhibitor 1 (PAI-1) has been linked to not only thrombosis and fibrosis but also to obesity and insulin resistance. Increased PAI-1 levels have been presumed to be consequent to obesity. We investigated the interrelationships of PAI-1, obesity, and insulin resistance in a high-fat/high-carbohydrate (HF) diet-induced obesity(More)
Peroxisome proliferator-activated receptors (PPARs): Novel therapeutic targets in renal disease. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-dependent transcription factors. PPARs play an important role in the general transcriptional control of numerous cellular processes, including(More)
Hyperphosphatemia is the major risk factor associated with vascular calcification (VC) in end-stage renal disease. As oxidative stress is increased in uremia, we studied the role of mitochondrial reactive oxygen species (ROS) and nuclear factor-κB signaling in phosphate-induced VC. In an in vitro calcification model (β-glycerophosphate (BGP) induction)(More)
Klotho is an anti-aging gene whose expression is regulated by many stimuli. Here we examined the transcriptional regulation of the klotho gene by peroxisome proliferator-activated receptor-gamma (PPAR-gamma). The PPAR-gamma agonists thiazolidinediones increased both klotho mRNA and protein expression in HEK293 cells and several renal epithelial cell lines.(More)
The dysfunction of pancreatic β-cell and the reduction in β-cell mass are the decisive events in the progression of type 2 diabetes. There is increasing evidence that cytokines play important roles in the procedure of β-cell failure. Cytokines, such as IL-1β, IFN-γ, TNF-α, leptin, resistin, adiponectin, and visfatin, have been shown to diversely regulate(More)
Objective—Endothelial activation is implicated in atherogenesis and diabetes. The role of peroxisome proliferator-activated receptor(PPAR) in endothelial activation remains poorly understood. In this study, we investigated the anti-inflammatory effect of PPARand the mechanism involved. Methods and Results—In human umbilical vein endothelial cells (HUVECs),(More)
Macula densa (MD) cells express COX-2 and COX-2-derived PGs appear to signal the release of renin from the renal juxtaglomerular apparatus, especially during volume depletion. However, the synthetic machinery and identity of the specific prostanoid released from intact MD cells remains uncertain. In the present studies, a novel biosensor tool was engineered(More)
Genetic disruption of the mouse EP4 receptor results in perinatal lethality associated with persistent patent ductus areteriosus (PDA). To circumvent this, an EP4 allele amenable to conditional deletion using the Cre/loxP system was generated. The targeting construct was comprised of a floxed exon2 in tandem with the neomycin-resistance gene in intron 2,(More)
UNLABELLED Pancreatic-derived factor (PANDER) is a pancreatic islet-specific cytokine that cosecretes with insulin and is important for β cell function. Here, we show that PANDER is constitutively expressed in hepatocytes, and its expression is significantly increased in steatotic livers of diabetic insulin-resistant db/db mice and mice fed a high-fat diet.(More)