Laboratory of Angiogenesis, Institute of Experimental Cardiology, National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation, Moscow, Russia.
V. A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russia.
Bull Exp Biol Med. 2022 May;173(1):5-9. doi: 10.1007/s10517-022-05480-9. Epub 2022 May 27.
It was suggested that the urokinase system plays a certain role in the regulation of activity of the endothelial-mesenchymal transition and in the development of perivascular fibrosis. Urokinase (uPA), the key component of the urokinase system, is a serine protease that binds to its receptor on the cell surface (uPAR) and affects the cell microenvironment components through the formation of plasmin, remodeling of the extracellular matrix, release of growth factors, and initiation of intracellular signals. The heart of PLAUR gene knockout C57BL/129 (uPAR-/-) mice showed signs of vasculopathy: reduced number of capillaries/arterioles, signs of endothelial-mesenchymal transition in endothelial cells, vascular wall remodeling, and deposition of extracellular matrix components. These changes were combined with enhanced expression of urokinase and active forms of TGF-β1. Apparently, uPAR is a part of a multicomponent system that provides multifaceted regulatory effects on the components of forming vessels and vascular wall cells, which allows considering it as a possible target for targeted antifibrotic therapy.
有人提出尿激酶系统在调节内皮-间充质转化活性和血管周围纤维化发展中起一定作用。尿激酶（uPA）是尿激酶系统的关键组成部分，是一种丝氨酸蛋白酶，与细胞表面的受体（uPAR）结合，并通过形成纤溶酶、重塑细胞外基质、释放生长因子和启动细胞内信号来影响细胞微环境成分。PLAUR 基因敲除 C57BL/129（uPAR-/-）小鼠的心脏表现出血管病变的迹象：毛细血管/小动脉数量减少、内皮细胞发生内皮-间充质转化的迹象、血管壁重塑以及细胞外基质成分的沉积。这些变化与尿激酶和 TGF-β1 的活性形式的表达增强有关。显然，uPAR 是一个多成分系统的一部分，它对形成血管和血管壁细胞的成分提供多方面的调节作用，这使得它可以被认为是一种可能的靶向抗纤维化治疗的靶点。
