@article {Kawai:2012::453,
title = "Matrix Metalloproteinase-9 Contributes to the Mobilization of Bone Marrow Cells in the Injured Liver",
journal = "",
parent_itemid = "",
publishercode ="",
year = "2012",
volume = "21",
number = "2-3",
publication date ="2012-02-01T00:00:00",
pages = "453-464",
itemtype = "ARTICLE",
url = "https://www.ingentaconnect.com/content/cog/ct/2012/00000021/f0020002/art00009",
doi = "doi:10.3727/096368911X605367",
keyword = "Chemokine ligand receptor 4 (CXCR4), Stromal-derived factor 1α (SDF-1α), Bone marrow (BM) transplantation, Lineage-negative cell, Chemokine ligand 12 (CXCL12)",
author = "Kawai, Kengo and Xue, Feng and Takahara, Terumi and Kudo, Hiroshi and Yata, Yutaka and Zhang, Wei and Sugiyama, Toshiro",
abstract = "Effective mobilization of hematopoietic stem cells (HSCs) in injured organs has not been established. Matrix metalloproteinase-9 (MMP-9) is known to release HSCs from bone marrow (BM) into the peripheral blood, but its role in the recruitment of HSCs to injured organs is unclear. In
this study we tried to clarify the role of the host MMP-9 in trafficking of HSCs toward the injured liver, especially the relation of MMP-9 with the chemokine receptor 4 (CXCR4)chemokine ligand 12 (CXCL12) axis, and to examine whether MMP-9 deficiency affects BM cell trafficking to
the injured liver in mice. In vitro, we investigated the effect of MMP-9 on migration activity and CXCR4 expression on lineage-negative (Lin) BM cells. In vivo, we induced acute and chronic liver injury in MMP-9 knockout (KO) and control mice by inoculation of carbon tetrachloride,
followed by transplantation of Lin BM cells obtained from enhanced green fluorescent protein (EGFP)-transgenic mice, and counted the BM cells mobilized in the injured liver. In a migration assay, active MMP-9, but not proMMP-9, increased the number of migrated Lin
BM cells, which was inhibited by tissue inhibitor of metalloproteinase-1 or a MMP inhibitor. This chemoattractant function by MMP-9 was synergistic when cotreated with CXCL12. CXCR4 expression on Lin BM cells was dose- and time-dependently increased by active MMP-9. At the
same time, treatment with MMP-9 enhanced CXCL12 expression, and CXCL12 reciprocally increased MMP-9 expression in BM cells. In in vivo studies, many EGFP+ cells were seen in control recipient mice. In contrast, few EGFP+ cells were observed in MMP-9 KO mice. BM cells
tended to differentiate into desmin+ cells. In conclusion, MMP-9 contributes to the mobilization of BM cells in the injured liver by upregulating the expression of CXCR4 on Lin BM cells and attracting BM cells along its gradient of CXCL12. Therefore, host MMP-9
plays an important role in BM cell migration in the injured liver.",
}