Loss of fibrinogen rescues mice from the pleiotropic effects of plasminogen deficiency
Loss of fibrinogen rescues mice from the pleiotropic effects of plasminogen deficiency
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DOI：
10.1016/s0092-8674(00)81390-2
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发表时间：
1996-11-15
期刊：
影响因子：
64.5
通讯作者：
Degen, JL
中科院分区：
文献类型：
--
作者：
Bugge, TH;Kombrinck, KW;Degen, JL
纤溶蛋白（原）是一种细胞外丝氨酸蛋白酶，与潜在生长因子和前胶原酶的激活、细胞外基质成分的降解和纤维蛋白清除有关。纤溶酶原（Plg）缺乏导致小鼠高死亡率、消瘦、自发性胃肠道溃疡、直肠脱垂和严重血栓形成。此外，plg缺陷小鼠在皮肤损伤后表现出伤口愈合延迟，这一缺陷部分与角质细胞迁移受损有关。我们制造了缺乏猪和纤维蛋白原（Fib）的小鼠，并表明从细胞外环境中去除纤维蛋白（原）减轻了以前与猪缺乏相关的各种自发病理，并纠正了愈合时间。缺乏猪和Fib的小鼠在表型上与缺乏纤维的小鼠难以区分。这些数据表明，猪的基本和可能唯一必要的生理作用是纤维溶解。
Plasmin(ogen) is an extracellular serine protease implicated in the activation of latent growth factors and procollagenase, degradation of extracellular matrix components, and fibrin clearance. Plasminogen (Plg) deficiency in mice results in high mortality, wasting, spontaneous gastrointestinal ulceration, rectal prolapse, and severe thrombosis. Furthermore, Plg-deficient mice display delayed wound healing following skin injury, a defect partly related to impaired keratinocyte migration. We generated mice deficient in Pig and fibrinogen (Fib) and show that removal of fibrin(ogen) from the extracellular environment alleviates the diverse spontaneous pathologies previously associated with Pig deficiency and corrects healing times. Mice deficient in Pig and Fib are phenotypically indistinguishable from Fib-deficient mice. These data suggest that the fundamental and possibly only essential physiological role of Pig is fibronolysis.