Microvessel formation from mouse aorta is stimulated in vitro by secreted VEGF
and extracts from metanephroi.
Akimoto, Tetsu, and Marc R. Hammerman.
George M. O'Brien Kidney and Urological Disease Center, Renal Division,
Departments of Medicine, Cell Biology, and Physiology, Washington University School
of Medicine, St. Louis, Missouri 63110
APStracts 10:0077C, 2003.
We have demonstrated that during culture under 5% O2, the addition of recombinant
human VEGF or FGF2 to mouse embryonic aorta explants (thoracic level to lateral
vessels supplying the mesonephros and metanephros) stimulates microvessel formation.
Here we show that microvessel formation is also stimulated by addition to explants of
supernatants obtained from metanephroi grown in serum-free organ culture or of
metanephroi extracts. Supernatants and extracts from metanephroi grown under hypoxic
conditions are more stimulatory than supernatants/extracts from metanephroi grown in
room air. VEGF and FGF2 can be detected by using immunohistochemistry in
developing nephrons in the cultured renal anlagen. Metanephroi supernatants contain
more VEGF if renal anlagen are grown under hypoxic conditions than if they are grown
in room air. Metanephros supernatant-stimulated microvessel formation is completely
inhibited by soluble sFlt-1 fusion protein or anti-VEGF antibodies (aVEGF). Extract-
stimulated microvessel formation is inhibited by aVEGF or anti-FGF2 antibodies, or
both. We conclude that metanephroi produce growth factors including VEGF and FGF
that enhance microvessel formation from embryonic thoracic aorta in vitro.
Received 20 September 2002; accepted in final form 14 February 2003
APS Manuscript Number C436-2.
Article publication pending Am J Physiol Cell Physiol
ISSN 1080-4757 Copyright 2003 The American Physiological Society.
Published in APStracts on 25 March 2003