Membrane-anchored plasminogen activator, urokinase receptor (MuPAR) and plasmin play key roles in regulating hematopoietic stem/progenitor cells (HSPCs) maintenance, homing, engraftment, and mobilization in the bone marrow, according to scientists at Katholieke Universiteit Leuven.
Using wild-type and genetically manipulated mice, they found that MuPAR is present on a subset of HSPCs and helps maintain this cell population in bone marrow. When MuPAR was deleted or inhibited, HSPC proliferation was increased and the ability of these cells to home and adhere to the bone marrow microenvironment was inhibited.
Additionally, MuPAR was inactivated by plasmin via proteolytic cleavage. This inactivation triggered HSPC mobilization.
Loss of the gene encoding MuPAR also impaired the ability of the HSPCs to repopulate the bone marrow in recipient mice.
The Journal of Clinical Investigation ran the article in its March 9 online early edition.