AJP - Renal Physiology, Vol 272, Issue 4 469-F476, Copyright © 1997 by American Physiological Society
Metanephric osteopontin regulates nephrogenesis in vitro
S. A. Rogers, B. J. Padanilam, K. A. Hruska, C. M. Giachelli and M. R. Hammerman
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Renal expression of osteopontin is enhanced in the setting of acute
ischemic injury. Because of the parallels that exist between recovery from
renal ischemia and renal development, we characterized the role that
osteopontin plays during metanephrogenesis in the rat. Osteopontin mRNA is
present in kidneys obtained from rat embryos as early as embryonic day 13
(E13). Immunohistochemical staining of metanephroi obtained from E16 rat
embryos and metanephroi obtained from E13 embryos and cultured for 3 days
in vitro demonstrated that osteopontin is expressed both in the developing
nephron and in the ureteric bud. Addition of anti-osteopontin antibodies to
metanephric organ cultures results in failure of the metanephric blastema
to undergo normal tubulogenesis. Addition of the arginine-glycine-aspartic
acid-containing peptide, cyclo-RGDfV, or the anti-alpha(v)beta3-integrin
antibody, LM609, to cultures has a similar effect. These findings establish
that osteopontin is produced within the rat metanephros during development
in vivo and suggest that the binding of osteopontin to the
alpha(v)beta3-integrin is required for tubulogenesis to occur in vitro.
Blastemal cells within metanephroi cultured in the presence of OP199
manifest increased apoptosis compared with controls. It is possible that
osteopontin plays an important anti-apoptotic role during the process of
metanephric blastema condensation that is a prerequisite for the formation
of nephrons in vivo.
