Dehydration impaired normal renal development in infant mice

The kidney is a major organ in which fluid balance and waste excretion is regulated. To obtain mature functions of the kidney, normal renal developmental processes need to be preceded. Comprehensive genetic programs underlying renal development during prenatal life have been widely studied. However, postnatal renal development, from infancy to juvenile period, have not been studied yet. Here, we investigated if structural and functional kidney development was still undergoing in early life by analyzing renal transcriptional networks of infant (4 weeks old) and juvenile (7 weeks old) mice. We further examined the effects of dehydration on kidney development. Kidneys at 4 weeks and 7 weeks old showed significantly distinctive functional network of genes. Gene sets related to cell cycle regulators and immature glomerular barrier integrity (COL4A1, COL4A2) were enriched in infantile kidneys while genes associated with ion transport and drug metabolism (CYP450 family) were shown in juvenile kidneys. Dehydration during infancy suppressed renal growth by interrupting SHH signaling pathway which targets cell cycle regulators. Importantly, disruption of developmental program ultimately led to long-term alterations in renal filtration function, by causing a decline in glomerular filtration barrier integrity. Taken together, we provide meaningful perspectives of renal development in infancy which suggests molecular and physiological background why infants are more vulnerable to dehydration than adults. These results provide new insights into the systemic effects of dehydration on renal development and may propose possible markers for clinical application in pediatric dehydration. Total RNA obtained from isolated kidneys subjected to water restriction for 1 week (RES 1W, 4-week-old) and 4 weeks (RES 4W, 7-week-old), and each group was compared to control group; CON 1W (4-week-old), CON 4W (7-week-old) respectively.