Involvement of the Reck tumor suppressor protein in maternal and embryonic vascular remodeling in mice

Ediriweera Ps Chandana,Rei Takahashi,Junseo Oh,Tomoko Matsuzaki,Yoko Yoshida,Akihiko Ueda,Hiroshi Kiyonari,Naoko Oshima,Satoshi Kawashima,Yasuhiko Tabata,Chiaki Takahashi,Makoto Noda,Mako Yamamoto,David B Alexander,Yasuhiro Maeda,Hitoshi Kitayama,Shunya Kondo

doi:10.1186/1471-213x-10-84

Abstract

BackgroundDevelopmental angiogenesis proceeds through multiple morphogenetic events including sprouting, intussusception, and pruning. Mice lacking the membrane-anchored metalloproteinase regulator Reck die in utero around embryonic day 10.5 with halted vascular development; however, the mechanisms by which this phenotype arises remain unclear.ResultsWe found that Reck is abundantly expressed in the cells associated with blood vessels undergoing angiogenesis or remodelling in the uteri of pregnant female mice. Some of the Reck-positive vessels show morphological features consistent with non-sprouting angiogenesis. Treatment with a vector expressing a small hairpin RNA against Reck severely disrupts the formation of blood vessels with a compact, round lumen. Similar defects were found in the vasculature of Reck-deficient or Reck conditional knockout embryos.ConclusionsOur findings implicate Reck in vascular remodeling, possibly through non-sprouting angiogenesis, in both maternal and embyornic tissues.

Highlights

Developmental angiogenesis proceeds through multiple morphogenetic events including sprouting, intussusception, and pruning
Reck is abundantly expressed in the cells associated with remodeling blood vessels in the mouse implantation chamber To gain insights into the functions of Reck in adult mice, we examined its tissue distribution by immunohistochemical techniques
RECK expression in these two cell types could be demonstrated by immunoblot assay using cultured human vascular endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs)

Summary

Introduction

Developmental angiogenesis proceeds through multiple morphogenetic events including sprouting, intussusception, and pruning. Mice lacking the membrane-anchored metalloproteinase regulator Reck die in utero around embryonic day 10.5 with halted vascular development; the mechanisms by which this phenotype arises remain unclear. Developmental angiogenesis proceeds through multiple morphogenetic events including sprouting, intussusception (splitting of pre-existing vessels by tissue pillars), and pruning [1,2,3]. Several key molecules in sprouting angiogenesis have been identified: e.g., vascular endothelial growth factor (VEGF) family members and their receptors, Notch and its ligand Delta-like ligand 4 (Dll4), and semaphorins and their receptors plexin/neuropilin complexes [4,5,6]. The mechanism by which certain blood vessels are selectively preserved during this highly destructive process is yet to be elucidated

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Conclusion