Plasminogen regulates stromal cell-derived factor-1/CXCR4-mediated hematopoietic stem cell mobilization by activation of matrix metalloproteinase-9.

ABSTRACT:

Objective

Granulocyte colony-stimulating factor (G-CSF) is a widespread therapeutic agent for stimulation of hematopoietic progenitor and stem cell (HPSC) mobilization from bone marrow (BM). Plasminogen (Plg) has been shown to be critical for HPSC mobilization. Here, we investigated the role of Plg in G-CSF-induced HPSC mobilization and the underlying mechanism.

Methods and results

By using gene-targeted mice, our data show that Plg is required for G-CSF-induced HPSC egress to sinusoidal capillaries in BM and subsequent mobilization to peripheral circulation. G-CSF induced Plg-dependent activation of matrix metalloproteinase-9 (MMP-9) in BM, and MMP-9 neutralization or deficiency suppressed HPSC migration and mobilization. Reconstitution of MMP-9 activity by BM transplantati

SUBMITTER: Gong Y 

PROVIDER: S-EPMC3159162 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature