Project description:In order to establish a rat embryonic stem cell transcriptome, mRNA from rESC cell line DAc8, the first male germline competent rat ESC line to be described and the first to be used to generate a knockout rat model was characterized using RNA sequencing (RNA-seq) analysis.
Project description:we assessed characteristic molecular and proteomic signatures in rat liver treated with drugs (pyrazinamide, ranitidine, enalapril, carbamazepine, and chlorpromazine) that are known to cause DILI in humans.
Project description:we assessed characteristic molecular and proteomic signatures in rat liver treated with drugs (pyrazinamide, ranitidine, enalapril, carbamazepine, and chlorpromazine) that are known to cause DILI in humans. In the present study, we assessed the characteristic gene expression signature for DILI in a rat model. Rats were administered representative drugs that are already known to induce DILI in humans and transcriptomic changes in rat liver were analyzed. The representative drugs, which induce three types (hepatocellular, mixed, and cholestatic) of DILI, that were used in this study were pyrazinamide (PZA, 150~1500 mg/kg), ranitidine (RAN, 209.5~2095 mg/kg), enalapril (ENA, 148.65~1486.5 mg/kg), carbamazepine (CBZ, 97.85~978.5 mg/kg), and chlorpromazine (CPZ, 7.1~71 mg/kg).
Project description:We created a rat renal congestion model and investigated the effect of renal congestion on hemodynamics and molecular mechanisms. The inferior vena cava (IVC) between the renal veins was ligated by suture in male Sprague-Dawley rats to increase upstream IVC pressure and induce congestion in the left kidney only. Left kidney congestion reduced renal blood flow, glomerular filtration rate, and increased renal interstitial hydrostatic pressure. Tubulointerstitial and glomerular injury and medullary thick ascending limb hypoxia were observed only in the congestive kidneys. Molecules related to extracellular matrix expansion, tubular injury, and focal adhesion were upregulated in microarray analysis. Renal decapsulation ameliorated the tubulointerstitial injury. Electron microscopy captured pericyte detachment in the congestive kidneys. Transgelin and platelet-derived growth factor receptors, as indicators of pericyte-myofibroblast transition, were upregulated in the pericytes and the adjacent interstitium. With the compression of the peritubular capillaries and tubules, hypoxia and physical stress induce pericyte detachment, which could result in extracellular matrix expansion and tubular injury in renal congestion.
