Characterization of renal transporter expression in mice during pregnancy, lactation, and type I diabetes

摘要: Renal transporters regulate the reabsorption and secretion of nutrients, drugs, toxicants. Modification their expression and/or activity can alter renal clearance, affecting drug efficacy toxicity. Prior work has suggested that sex hormones metabolic changes, like diabetes obesity, transporter in rodents. The purpose this thesis was to characterize mRNA protein uptake efflux potential regulatory transcription factors response gestation, lactation, type I female C57BL/6 mice. In a time-course study, kidney were evaluated using qPCR, western blot, immunofluorescence staining on gestation days (GD) 7, 11, 14, 17 postnatal (PD) 1, 15, 30. Pregnancy caused marked down-regulation apical Mdr1b, Mrp2, Mrp4, Mate1 up-regulation basolateral Mrp3. Mdr1b Mrp4 decreased early pregnancy remained low throughout lactation whereas Mrp1, did not begin decline until mid-gestation. A increase Mrp3 observed at Western blot confirmed reduced Mrp2 elevated levels pregnant For diabetic mice treated repeatedly with intraperitoneal doses vehicle or streptozotocin (STZ) induce diabetes. After two weeks hyperglycemia, STZ-and vehicle-treated control mated overnight tissues collected 14 later. Both differentially regulated STZ treatment. Oat2, Oat5, Oatp2b1, Oatp4c1, Pept1, Mrp5. had little effect STZ-mediated Oat2 Oat5 mRNA, but prevent Oatp4c1 mRNA. both studies, profiling revealed (AhR, PXR, HNF1α, PPARα Nrf2) might participate regulating expression. Taken together, these results suggest transport signaling pathways are altered by endocrine changes occur during