title: Regulation of soluble neuropilin 1, an endogenous angiogenesis inhibitor, in liver development and regeneration.
abstract: Neuropilin-1 (NRP1) is a receptor for vascular endothelial growth factor (VEGF). A soluble isoform of Nrp1 (sNrp1) has not been described in the mouse. Our goal was to examine the expression of mouse sNrp1 during liver development and regeneration.sNrp1 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 immunohistochemical analyses. HGF/NRP1 binding was examined in vitro.A novel 588-amino acid sNrp1 isoform was found to contain the ligand binding regions of Nrp1. The adult liver expressed more sNrp1 than full-length Nrp1. In vivo, hepatocytes constitutively expressed VEGF and sNrp1 in the quiescent state. sNrp1 was highly up-regulated at P20, a time point coinciding with a plateau in liver and body weights. Following hepatectomy, endogenous levels of sNrp1 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 sNRP1.We cloned a novel mouse sNrp1 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.
authors: 1Vascular Biology Program, Boston Children's Hospital 2Department of Surgery, Harvard Medical School 3Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, MA, United States 4Department of Surgery, Klinikum Grosshadern, LMU Munich, Munich, Germany 5Department of Ophthalmology, Harvard Medical School 6Department of Pathology, Harvard Medical School 7Schepens Eye Research Institute, Massachusetts Eye & Ear, Boston, MA, United States.
authors: Dipak
authors: D
authors: Panigrahy
authors: Irit
authors: I
authors: Adini
authors: Roni
authors: R
authors: Mamluk
authors: Nicholas
authors: N
authors: Levonyak
authors: Christiane J
authors: CJ
authors: Bruns
authors: Patricia A
authors: PA
authors: D'Amore
authors: Michael
authors: M
authors: Klagsbrun
authors: Diane R
authors: DR
authors: Bielenberg
mesh_terms: D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008099:Liver / Q000254:growth & development* / Q000378:metabolism*; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000502:physiology*; D039942:Neuropilin-1 / Q000096:biosynthesis*; D012689:Sequence Homology, Nucleic Acid; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D039942:Neuropilin-1