A Novel Rat Model with Podocyte Injury in Developing Stage Glomeruli

Recent investigations have revealed that growth in utero might be an important determinant of adult disorders. The number of nephrons in humans is determined in utero. It is reported that infants who show signs of intrauterine growth retardation (IUGR) at birth have a significant reduction in nephron number and have a high risk for several kidney diseases. The glomerular epithelial cell (podocyte) plays a critical role in maintaining the function and the tuft architecture of glomeruli. In this study, we aimed to establish a rat model with podocyte injury in the developing stage. Five-day-old rats were treated with puromycin aminonucleoside (PAN), which is accepted to have toxicity to podocytes since glomerular maturation lasts after birth in rats, and 5-day-old rats correspond to the late gestational stage in humans. Podocyte injury and its maturity were assessed by the staining of the podocyte functional molecules, nephrin and podocin. In the normal infant rats, nephrin and podocin in podocytes are observed in a continuous linear pattern at the early capillary loop stage. At 24 h after PAN injection, the staining of nephrin and podocin at this stage of glomeruli shifted to a discontinuous pattern, and their staining intensity clearly decreased. Podocyte injury suffered at developing stage of glomeruli resulted in the reduction of podocyte numbers, the compensatory glomerular hypertrophy, and the retardation of any increase in body weight. The model could serve as a mimic of infants who evidence signs of IUGR at birth. The model is suitable to investigate the relation between podocyte injury suffered at the early developing stage and the risk for several kidney diseases in adulthood.