Reduction in fibrotic tissue formation in mice genetically deficient in plasminogen activator inhibitor-1
Reduction in fibrotic tissue formation in mice genetically deficient in plasminogen activator inhibitor-1
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DOI：
10.1016/s0002-9440(10)63674-7
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发表时间：
2003-08-01
影响因子：
6
通讯作者：
Simon, RH
中科院分区：
文献类型：
--
作者：
Chuang-Tsai, S;Sisson, TH;Simon, RH
纤溶酶原激活物抑制物-1基因(PAI-1(-/-))纯合子缺失的小鼠相对免受博莱霉素诱导的肺纤维化的影响。至少部分保护作用似乎发生在病理过程的后期，此时纤维组织正在沉积。为了研究PAI-1缺乏对纤维化的影响，我们研究了皮下植入的聚乙烯醇海绵中纤维组织的积聚。与PAI-1缺乏对博莱霉素诱导的肺纤维化的影响类似，与野生型小鼠相比，PAI-1(-/-)组植入的海绵中纤维组织的积累速度更慢。在PAI-1(-/-)小鼠身上观察到的另一个显著不同是，在野生型和PAI-1(-/-)小鼠中，植入后1天，海绵中形成的富含纤维蛋白的基质迅速被去除。结缔组织侵袭的模式也不同：野生型小鼠的细胞以单独穿透细胞的形式渗透，而在PAI-1(-/-)小鼠中，它们作为明确划分的前进前沿进行渗透。通过在植入前用低浓度的胶原浸泡海绵来提供替代的临时基质，纠正了PAI-1缺乏引起的变化。总而言之，PAI-1缺乏似乎部分地通过改变组织损伤后不久形成的临时基质来影响纤维组织的形成。
Mice with homozygous deletion of the plasminogen activator inhibitor-1 gene (PAI-1(-/-)) are relatively protected from bleomycin-induced pulmonary fibrosis. At least part of the protective effect appears to occur during the latter stages of the pathological process when fibrotic tissue is being deposited. To investigate the effect of PAI-1 deficiency on fibrosis, we studied the accumulation of fibrotic tissue within subcutaneously implanted polyvinyl alcohol sponges. Similar to the effect of PAI-1 deficiency on bleomycin-induced pulmonary fibrosis, the accumulation of fibrotic tissue within implanted sponges occurred more slowly in PAI-1(-/-) compared to wild-type mice. Another striking difference observed in the PAI-1(-/-) mice was the rapid removal of a fibrin-rich matrix that formed within the sponges by 1 day after implantation in both wild-type and PAI-1(-/-) mice. The pattern of connective tissue invasion also differed: cells in wild-type mice infiltrated as individually penetrating cells whereas in PAI-1(-/-) mice they did so as a well-demarcated advancing front. Providing an alternative provisional matrix by impregnating sponges with a low concentration of collagen before implantation corrected the changes induced by PAI-1 deficiency. In conclusion, PAI-1 deficiency appears to affect fibrotic tissue formation in part by altering the provisional matrix that forms soon after tissue injury.