Plasminogen deficiency results in poor clearance of non-fibrin matrix and persistent activation of hepatic stellate cells after an acute injury

Vicky Lee Ng, Gregg E. Sabla, Hector Melin-Aldana, Nancy Kelley-Loughnane, Jay L. Degen, Jorge A. Bezerra*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Background/Aims: Plasminogen directs matrix proteolysis during liver repair. Based on the role of hepatic stellate cells (HSCs) on matrix production, we investigated whether plasminogen-driven matrix proteolysis modulates the phenotype of HSCs. Methods: Carbon tetrachloride was injected intraperitoneally into mice deficient in plasminogen, fibrinogen, or both, and to normal littermates, followed by determination of the phenotype of HSCs, matrix deposition, and apoptosis. Results: Activation of HSCs was restricted to the zone of injury and increased >ten-fold above baseline regardless of the plasminogen status 2 days after toxin. Thereafter, the number of activated HSCs decreased to baseline levels between 7 and 14 days in normal mice, but remained elevated in plasminogen-deficient livers ∼ten-fold above non-targeted littermates. Despite the zonal increase in activated HSCs, the total number of desmin-stained HSCs was similar along the Iobule in both genotypes. No appreciable difference in apoptosis of perisinusoidal cells was found between genotypes; however, fibrillary material was present in the subsinusoidal space of Plg0 livers. This fibrillary material was not fibrin, as demonstrated by similar findings in Plg0/Fib0 mice, which accumulated fibronectin in injured areas. Conclusions: Proteolytic clearance of non-fibrin matrix components by plasminogen must occur for HSCs to restore the quiescent phenotype during liver repair.

Original languageEnglish (US)
Pages (from-to)781-789
Number of pages9
JournalJournal of Hepatology
Volume35
Issue number6
DOIs
StatePublished - Dec 1 2001

Keywords

  • Hepatocyte
  • Liver
  • Matrix
  • Regeneration
  • Repair

ASJC Scopus subject areas

  • Hepatology

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