Renal budding (left) increases when endostatin is inhibited (right).


Anew study identifies a possible new function for endostatin, the potential cancer-killer that checks blood vessel growth.Within the developing kidney, endostatin may help regulate the branching that establishes the network of urine-collecting tubules.

Cells in the ureteric bud divide and change shape to form the plumbing system of the kidney. Because endostatin inhibits blood vessel formation, Lloyd Cantley (Yale University, New Haven, CT) and colleagues suspected that it might also limit the formation of new tubules within the ureteric bud. To find out, they grew ureteric bud tissue in culture, adding exogenous endostatin or blocking endogenous production.

The results were striking. “Endostatin has a profound effect on branching,” says Cantley. The authors found that ureteric bud tissue branches excessively if doused with an anti- endostatin antibody. Buds treated with antibody, for instance, sprouted 75% more branches than the control group. By contrast, adding endostatin to the ureteric bud hampers branch formation. Earlier studies had shown that inactivation of glypican-3, a receptor for endostatin as well as heparin-binding growth factors, results in excessive proliferation and branching of the ureteric bud. These studies identified bone morphogenetic protein as one of the possible regulators of branching in the ureteric bud. This paper adds endostatin to the list, Cantley says. He adds that endostatin's role in the kidneys may not be limited to development; it may also help repair injuries. ▪


Karihaloo, A., et al.
Proc. Natl. Acad. Sci. USA.