Plasmin-mediated proteolysis is required for hepatocyte growth factor activation during liver repair

Kumar Shanmukhappa, Ursula Matte, Jay L. Degen, Jorge A. Bezerra

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


The physiological relevance of the activation of hepatocyte growth factor (Hgf) by the plasminogen (Plg) system of proteases and its contribution to tissue repair are largely undefined. Here, we investigated whether the defective liver repair in mice lacking Plg is due to impaired activation of Hgf. Loss of Plg in vivo suppressed Hgf activation and signaling through its Met tyrosine kinase receptor. Without Plg, hepatocytes were unresponsive to Hgf-induced proliferation and migration, with a more pronounced impairment in hepatocyte movement within the hepatic environment. Most notably, circumventing the defect in proteolytic activation of Hgf by the downstream expression of an activated Met receptor corrected the functional deficits and improved liver repair in Plg-deficient mice. These findings support a fibrinolysis-unrelated role for Plg in modulating cell proliferation and migration by activation of Hgf.

Original languageEnglish (US)
Pages (from-to)12917-12923
Number of pages7
JournalJournal of Biological Chemistry
Issue number19
StatePublished - May 8 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Plasmin-mediated proteolysis is required for hepatocyte growth factor activation during liver repair'. Together they form a unique fingerprint.

Cite this