TY - JOUR
T1 - Plasminogen deficiency leads to impaired remodeling after a toxic injury to the liver
AU - Bezerra, Jorge A.
AU - Bugge, Thomas H.
AU - Melin-Aldana, Hector
AU - Sabla, Gregg
AU - Kombrinck, Keith W.
AU - Witte, David P.
AU - Degen, Jay L.
PY - 1999/12/21
Y1 - 1999/12/21
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.96.26.15143
DO - 10.1073/pnas.96.26.15143
M3 - Article
C2 - 10611352
AN - SCOPUS:0033592863
SN - 0027-8424
VL - 96
SP - 15143
EP - 15148
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 26
ER -