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Plasminogen is essential for granulation tissue formation during the recovery process after liver injury in mice
Author(s) -
KAWAO N.,
NAGAI N.,
ISHIDA C.,
OKADA K.,
OKUMOTO K.,
SUZUKI Y.,
UMEMURA K.,
UESHIMA S.,
MATSUO O.
Publication year - 2010
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2010.03870.x
Subject(s) - granulation tissue , process (computing) , liver injury , chemistry , medicine , wound healing , surgery , computer science , operating system
Summary. Background: The involvement of plasminogen in liver repair has been reported, but its exact role in promoting this process is unknown. Objective: To elucidate the underlying mechanism, we examined the dynamics of liver repair by using a reproducible liver injury model in plasminogen gene‐deficient mice and their wild‐type littermates. Methods: Liver injury was induced by photochemical reaction and the subsequent responses were histologically analyzed. Results: In wild‐type animals, the area of the damage successively decreased, and the repair process was associated with macrophage accumulation at its border. Neutrophils were also attracted to the damaged region on day 1 and were evident only at its border by day 4, which spatially and temporally coincided with the expression of macrophage chemoattractant protein‐1 (MCP‐1). Neutrophil depletion suppressed recruitment of macrophages at the border between the damaged and the normal tissues. These changes were followed by activated hepatic stellate cell accumulation, collagen fiber deposition and angiogenesis at the boundaries of the injured zone. In contrast, in plasminogen gene‐deficient mice, the decrease in the area of damage, macrophage accumulation, late‐phase neutrophil recruitment, hepatic stellate cell accumulation, collagen fiber deposition and angiogenesis were all impaired. Conclusion: Our data suggest that accumulated neutrophils at the border of the damaged area may contribute to macrophage accumulation at granulation tissue via the production of MCP‐1 after liver injury. The plasminogen system is critical for liver repair by facilitating macrophage accumulation and triggering a cascade of subsequent repair events.