Plasminogen deficiency leads to impaired remodeling after a toxic injury to the liver

Jorge A. Bezerra*, Thomas H. Bugge, Hector Melin-Aldana, Gregg Sabla, Keith W. Kombrinck, David P. Witte, Jay L. Degen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

Abstract

Cellular proliferation and tissue remodeling are central to the regenerative response after a toxic injury to the liver. To explore the role of plasminogen in hepatic tissue remodeling and regeneration, we used carbon tetrachloride to induce an acute liver injury in plasminogen-deficient (Plg°) mice and nontransgenic littermates (Plg+). On day 2 after CCl4, livers of Plg+ and Plg°mice had a similar diseased pale/lacy appearance, followed by restoration of normal appearance in Plg+ livers by day 7. In contrast, Plg°livers remained diseased for as long as 2.5 months, with a diffuse pale/lacy appearance and persistent damage to centrilobular hepatocytes. The persistent centrilobular lesions were not a consequence of impaired proliferative response in Plg°mice. Notably, fibrin deposition was a prominent feature in diseased centrilobular areas in Plg°livers for at least 30 days after injury. Nonetheless, the genetically superimposed loss of the Aα fibrinogen chain (Plg°/Fib°mice) did not correct the abnormal phenotype. These data show that plasminogen deficiency impedes the clearance of necrotic tissue from a diseased hepatic microenvironment and the subsequent reconstitution of normal liver architecture in a fashion that is unrelated to circulating fibrinogen.

Original languageEnglish (US)
Pages (from-to)15143-15148
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number26
DOIs
StatePublished - Dec 21 1999

ASJC Scopus subject areas

  • General

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