Effect of retinoic acid on renal development in newborn mice treated with an angiogenesis inhibitor

Abstract

Background: A mouse model of impaired renal development was developed and the effect of retinoic acid (RA) was investigated in this animal model. Methods: An angiogenesis inhibitor (SU1498) was injected s.c. into day 3 C57BL/6 newborn mice to create a model of arrested renal development. RA (2 mg/kg) was injected i.p. for 10 days. Morphometry and immunohistochemistry were done. Results: Mice injected with SU1498 demonstrated deranged renal development in tubular structure and glomerular tuft area. Cortical thickness and area of glomerular tuft were significantly decreased after vascular endothelial growth factor (VEGF) inhibitor, and were significantly restored by RA. The length of capillary loops/glomerulus, the number of podocytes/glomerulus, and density of peritubular capillaries on CD31 immunostaining were significantly decreased by VEGF blocking and recovered by RA. Conclusions: VEGF plays a major role in renal development, and RA reverses the inhibited development caused by an angiogenesis inhibitor. © 2010 Japan Pediatric Society.