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J Hepatol. 2001 Dec;35(6):781-9.

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

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  • 1Divisions of Gastroenterology, Hepatology, and Nutrition, Children's Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229-3039, USA.

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 approximately ten-fold above non-targeted littermates. Despite the zonal increase in activated HSCs, the total number of desmin-stained HSCs was similar along the lobule 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 Plg(0) livers. This fibrillary material was not fibrin, as demonstrated by similar findings in Plg(0)/Fib(0) 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.

PMID:
11738106
[PubMed - indexed for MEDLINE]
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