Regulation of soluble neuropilin 1, an endogenous angiogenesis inhibitor, in liver development and regeneration

SummaryNeuropilin-1 (NRP1) is a receptor for vascular endothelial growth factor (VEGF). A soluble isoform of Nrp1 (sNrpI) has not been described in the mouse. Our goal was to examine the expression of mouse sNrpI during liver development and regeneration. sNrpI was cloned from mouse liver. The expression of sNrp1 and VEGF was examined in mouse liver during post-natal development and regeneration using northern blot, western blot, in situ hybridisation, and immunohis-tochemical analyses. HGF/NRP1 binding was examined in vitro. A novel 588-amino acid sNrpI isoform was found to contain the ligand binding regions of Nrp1. The adult liver expressed more sNrp1 than full-length Nrp1. In vivo, hepato-cytes constitutively expressed VEGF and sNrpI in the quiescent state. sNrpI was highly up-regulated at P20, a time point coinciding with a plateau in liver and body weights. Following hepatectomy endogenous levels of sNrpI decreased during the rapid growth phase, and VEGF levels were highest just prior to and during the angiogenic phase. sNrp1 levels again rose 5–10 days post-hepatectomy presumably to control regeneration. HGF protein bound NRP1 and binding was competed with sNRPL We cloned a novel mouse sNrpI isoform from liver and provide evidence that this endogenous angiogenesis inhibitor may regulate VEGF or HGF bioavailability during normal physiological growth and development as well as during liver regeneration.