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



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.


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.


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.


Proteolytic clearance of non-fibrin matrix components by plasminogen must occur for HSCs to restore the quiescent phenotype during liver repair.

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