The Absence of uPAR Is Associated with the Progression of Dermal Fibrosis
The Absence of uPAR Is Associated with the Progression of Dermal Fibrosis
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DOI：
10.1038/jid.2008.157
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发表时间：
2008-12-01
影响因子：
6.5
通讯作者：
Matsuno, Hiroyuki
中科院分区：
文献类型：
--
作者：
Kanno, Yosuke;Kaneiwa, Aki;Matsuno, Hiroyuki
纤维蛋白溶解系统被认为在细胞外基质（ECM）的降解中起重要作用。然而，关于该系统如何影响纤维化的详细机制仍不清楚。尿激酶型纤溶酶原激活物受体（uPAR）不仅作为蛋白酶受体发挥作用，而且通过细胞内信号传导在细胞粘附、分化、增殖和迁移中发挥作用。为了研究uPAR对真皮纤维化的作用，将野生型小鼠的皮肤与uPAR缺陷（uPAR（-/-））小鼠的皮肤进行比较。结果表明，uPAR的缺乏增加了真皮厚度。此外，uPAR（-/-）小鼠皮肤中的胶原合成以及肌成纤维细胞的数量大于uPAR（+/+）小鼠皮肤中的胶原合成以及肌成纤维细胞的数量。此外，我们发现uPAR的缺乏减弱了皮肤中基质金属蛋白酶（MMP）-2，9的活性。总之，这项研究表明，uPAR的缺乏不仅调节纤维化相关基因的表达和MMP活性，但也导致ECM沉积。因此，uPAR的缺乏诱导真皮纤维化。这些发现为uPAR在真皮纤维化中的作用提供了新的见解。
The fibrinolytic system is considered to play an important role in the degradation of extracellular matrices (ECM). However, the detailed mechanism regarding how this system affects fibrosis remains unclear. Urokinase-type plasminogen activator receptor (uPAR) not only functions as a proteinase receptor but also plays a role in cellular adhesion, differentiation, proliferation, and migration through intracellular signaling. To investigate the effect of uPAR on dermal fibrosis, the skin of wild-type mice was compared with uPAR-deficient (uPAR(-/-)) mice. The results showed that the absence of uPAR increases dermal thickness. In addition, collagen synthesis as well as the number of myofibroblasts was greater in the skin of uPAR(-/-) mice than in the skin of uPAR(+/+) mice. Moreover, we showed that the absence of uPAR attenuates the activity of matrix metalloproteinases (MMP)-2, 9 in the skin. In conclusion, this study suggests that the absence of uPAR not only regulates fibrosis-related gene expression and MMP activity but also results in ECM deposition. Therefore, the absence of uPAR induces dermal fibrosis. These findings provide new insights into the role of uPAR on dermal fibrosis.