Endostatin regulates branching morphogenesis of renal epithelial cells and ureteric bud.
Endostatin (ES) inhibits endothelial cell migration and has been found to bind to glypicans (Gpcs) on both endothelial cells and renal epithelial cells. We examined the possibility that ES might regulate epithelial cell morphogenesis. The addition of ES to cultured epithelial cells causes an inhibition of both hepatocyte growth factor- and epidermal growth factor-dependent process formation and migration. In contrast, ES does not inhibit epidermal growth factor-dependent morphogenesis in renal epithelial cells derived from Gpc-3 -/mice, whereas expression of Gpc-1 in these cells reconstitutes ES responsiveness. Gpc-3 -/mice have been shown to display enhanced ureteric bud (UB) branching early in development, and cultured UB cells release ES into the media, suggesting that ES binding to Gpcs may regulate UB branching. The addition of ES inhibits branching of the explanted UB, whereas a neutralizing Ab to ES enhances UB outgrowth and branching. Thus, local expression of ES at the tips of the UB may play a role in the regulation of UB arborization.
Karihaloo
A
A
Section of Nephrology, Yale University School of Medicine, 333 Cedar Street, LMP 2093, New Haven, CT 06520, USA. anil.karohaloo@yale.edu
Karumanchi
S A
SA
Barasch
J
J
Jha
V
V
Nickel
C H
CH
Yang
J
J
Grisaru
S
S
Bush
K T
KT
Nigam
S
S
Rosenblum
N D
ND
Sukhatme
V P
VP
Cantley
L G
LG
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000502:physiology*; D043169:Endostatins; D004815:Epidermal Growth Factor / Q000494:pharmacology; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans / Q000032:analysis / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D007668:Kidney / Q000196:embryology*; D051379:Mice; D009024:Morphogenesis; D010446:Peptide Fragments / Q000502:physiology*; D051381:Rats; D014513:Ureter / Q000196:embryology*
D043169:Endostatins; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D010446:Peptide Fragments; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D003094:Collagen