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纤维蛋白原的缺失使小鼠从纤溶酶原缺乏的多效性影响中获救。

Loss of fibrinogen rescues mice from the pleiotropic effects of plasminogen deficiency.

作者信息

Bugge T H, Kombrinck K W, Flick M J, Daugherty C C, Danton M J, Degen J L

机构信息

Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.

出版信息

Cell. 1996 Nov 15;87(4):709-19. doi: 10.1016/s0092-8674(00)81390-2.

DOI:10.1016/s0092-8674(00)81390-2
PMID:8929539
Abstract

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 Plg and fibrinogen (Fib) and show that removal of fibrin(ogen) from the extracellular environment alleviates the diverse spontaneous pathologies previously associated with Plg deficiency and corrects healing times. Mice deficient in Plg and Fib are phenotypically indistinguishable from Fib-deficient mice. These data suggest that the fundamental and possibly only essential physiological role of Plg is fibrinolysis.

摘要

纤溶酶(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以及纤维蛋白清除有关。小鼠纤溶酶原(Plg)缺乏会导致高死亡率、消瘦、自发性胃肠道溃疡、直肠脱垂和严重血栓形成。此外,Plg缺乏的小鼠在皮肤损伤后伤口愈合延迟,这一缺陷部分与角质形成细胞迁移受损有关。我们培育出了Plg和纤维蛋白原(Fib)缺乏的小鼠,并表明从细胞外环境中去除纤维蛋白(原)可减轻先前与Plg缺乏相关的各种自发性病理状况,并纠正愈合时间。Plg和Fib缺乏的小鼠在表型上与Fib缺乏的小鼠无法区分。这些数据表明,Plg的基本且可能唯一重要的生理作用是纤维蛋白溶解。

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Loss of fibrinogen rescues mice from the pleiotropic effects of plasminogen deficiency.纤维蛋白原的缺失使小鼠从纤溶酶原缺乏的多效性影响中获救。
Cell. 1996 Nov 15;87(4):709-19. doi: 10.1016/s0092-8674(00)81390-2.
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Skin wound healing in MMP2-deficient and MMP2 / plasminogen double-deficient mice.基质金属蛋白酶 2 缺陷型和基质金属蛋白酶 2/纤溶酶原双重缺陷型小鼠的皮肤伤口愈合。
Exp Dermatol. 2010 Aug;19(8):e234-40. doi: 10.1111/j.1600-0625.2009.01062.x.
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J Invest Dermatol. 2008 Aug;128(8):2092-101. doi: 10.1038/jid.2008.54. Epub 2008 Mar 13.
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Plasminogen deficiency causes severe thrombosis but is compatible with development and reproduction.纤溶酶原缺乏会导致严重血栓形成,但与发育和繁殖相容。
Genes Dev. 1995 Apr 1;9(7):794-807. doi: 10.1101/gad.9.7.794.
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Absence of functional compensation between coagulation factor VIII and plasminogen in double-knockout mice.双重基因敲除小鼠凝血因子 VIII 和纤溶酶原之间不存在功能代偿。
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Plasminogen deficiency leads to impaired lobular reorganization and matrix accumulation after chronic liver injury.纤溶酶原缺乏会导致慢性肝损伤后小叶重组受损和基质积累。
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The plasminogen receptor, Plg-R, plays a role in inflammation and fibrinolysis during cutaneous wound healing in mice.纤溶酶原受体(Plg-R)在小鼠皮肤创伤愈合过程中的炎症和纤维蛋白溶解中发挥作用。
Cell Death Dis. 2020 Dec 12;11(12):1054. doi: 10.1038/s41419-020-03230-1.

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