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uPA and macrophages in muscle regeneration
Author(s) -
Novak Margaret L,
Nguyen MaiHuong,
Cheng Ming,
Sisson Thomas H,
Koh Timothy J
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.801.34
Subject(s) - macrophage , regeneration (biology) , microbiology and biotechnology , plasminogen activator , urokinase receptor , skeletal muscle , biology , urokinase , in vitro , endocrinology , biochemistry , genetics
The plasminogen system and macrophages play important roles in tissue repair following injury. Mice deficient in the urokinase‐type plasminogen activator (uPA) exhibit impaired accumulation of macrophages following muscle injury and severely impaired muscle fiber regeneration. We hypothesized that macrophage expression of uPA promotes macrophage migration into damaged muscle and subsequent muscle regeneration. To test this hypothesis, we cross‐bred macrophage‐specific uPA overexpressing mice with uPA null mice to generate mice that express uPA only in macrophages. Such macrophage‐only uPA expression was sufficient to restore uPA activity, macrophage accumulation and muscle fiber regeneration in otherwise uPA null mice. In addition, macrophage‐specific overexpression of uPA appears to enhance muscle fiber regeneration in wild‐type mice. In vitro studies demonstrated that uPA promotes macrophage migration through both proteolytic and non‐proteolytic mechanisms, which may include the proteolytic activation of HGF. We also found that uPA promotes myoblast proliferation in vitro through its proteolytic activity and this process was inhibited by an HGF blocking antibody. In summary, macrophage expression of uPA plays a critical role in muscle regeneration. Supported by the Department of Defense Peer Reviewed Medical Research Program.