Plasminogen deficiency leads to impaired remodeling after a toxic injury to the liver
Plasminogen deficiency leads to impaired remodeling after a toxic injury to the liver
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DOI：
10.1073/pnas.96.26.15143
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发表时间：
1999-12-21
影响因子：
11.1
通讯作者：
Degen, JL
中科院分区：
文献类型：
--
作者：
Bezerra, JA;Bugge, TH;Degen, JL
细胞增殖和组织重塑是肝脏毒性损伤后再生反应的核心。为了探讨纤溶酶原在肝组织重塑和再生中的作用，我们使用四氯化碳诱导纤溶酶原缺陷（Plg度）小鼠和非转基因同窝小鼠（Plg（+））的急性肝损伤。在CCl 4后第2天，Plg（+）和Plg程度小鼠的肝脏具有相似的患病苍白/花边外观，随后在第7天Plg（+）肝脏中恢复正常外观。相比之下，Plg degree肝脏在长达2.5个月的时间内仍然存在病变，表现为弥漫性苍白/花边状外观和小叶中心肝细胞的持续性损伤。持续性小叶中心病变不是Plg degree小鼠增殖反应受损的结果。值得注意的是，纤维蛋白沉积是一个突出的特点，在病变的小叶中心区在Plg度肝脏至少30天后受伤。尽管如此，A α纤维蛋白原链的遗传叠加损失（Plg度/Fib度小鼠）并没有纠正异常表型。这些数据表明，纤溶酶原缺乏阻碍了坏死组织从患病肝脏微环境中的清除，以及随后以与循环纤维蛋白原无关的方式重建正常肝脏结构。
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 degrees) mice and nontransgenic littermates (Plg(+)). On day 2 after CCl4, livers of Plg(+) and Plg degrees mice had a similar diseased pale/lacy appearance, followed by restoration of normal appearance in Plg(+) livers by day 7. In contrast, Plg degrees 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 degrees mice. Notably, fibrin deposition was a prominent feature in diseased centrilobular areas in Plg degrees livers for at least 30 days after injury. Nonetheless, the genetically superimposed loss of the A alpha fibrinogen chain (Plg degrees/Fib degrees 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.