Liver-Derived Matrix Metalloproteinase-9 (Gelatinase B) Recruits Progenitor Cells from Bone Marrow into the Blood Circulation

• Published in: Biological & pharmaceutical bulletin Vol. 26; no. 4; pp. 564 - 568
• Main Authors: Watanabe, Yoshifumi, Haruyama, Takahiro, Akaike, Toshihiro
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01-04-2003; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Biological and medical sciences; Blood Circulation - physiology; bone marrow; Bone Marrow Cells - enzymology; Enzyme Induction - physiology; Female; Gene Expression Regulation, Enzymologic - physiology; hematopoietic progenitor cell; Hematopoietic Stem Cells - enzymology; hepatitis; liver; Liver - enzymology; Liver - pathology; matrix metalloproteinase (MMP)-9; Matrix Metalloproteinase 9 - biosynthesis; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - physiology; Medical sciences; Mice; Mice, Inbred BALB C; recruitment; hematopoietic progenitor cell; matrix metalloproteinase (MMP)-9; hepatitis; liver; recruitment; bone marrow
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.26.564

Matrix metalloproteinases (MMPs) are involved in invasive cell behavior, embryonic development and organ remodeling. In this report, we investigated the role of liver-derived MMP-9 in the in vivo system at liver injury. Liver injury induced MMP-9 expression in the liver 3 to 12 h after intravenous administration of anti-Fas antibody, followed by the expression of the activity and the protein detected by zymography and Western blotting, respectively, in the blood circulation. Interestingly, the MMP-9 expression was accompanied by the recruitment of hematopoietic progenitor cells from bone marrow into the circulation. The recruitment was blocked by a specific MMP-9 inhibitor, R94138, which did not affect the Fas-mediated liver injury or induced expression of MMP-9. Compulsive expression of mutant active MMP-9 in the liver also recruited the progenitor cells into the circulation. In contrast, partial hepatectomy, which treatment does not directly injure hepatocytes, did not recruit progenitor cells despite the increased expression of MMP-9 in the circulation. These results suggest that liver-derived MMP-9 induced by liver injury plays an essential role in the recruitment of hematopoietic progenitor cells from bone marrow into the blood circulation.