Thrombin stimulates fibroblast-mediated collagen lattice contraction by its proteolytically activated receptor.
Thrombin stimulates fibroblast-mediated collagen lattice contraction by its proteolytically activated receptor.
复制标题
凝血酶通过其蛋白水解激活受体刺激成纤维细胞介导的胶原蛋白晶格收缩。
DOI：
10.1006/excr.1994.1100
复制
发表时间：
1994
影响因子：
3.7
通讯作者：
Tomasek,JJ
中科院分区：
文献类型：
--
作者：
Pilcher,BK;Kim,DW;Carney,DH;Tomasek,JJ
提出成纤维细胞收缩在诸如伤口愈合的事件期间的组织收缩中起重要作用。凝血酶被认为可以促进成纤维细胞产生力;然而，其细胞外作用模式尚不清楚。本研究的目的是在体外胶原晶格收缩试验中，确定凝血酶及其受体的激活在促进人成纤维细胞收缩中的作用。人α-凝血酶以剂量依赖性方式促进成纤维细胞收缩，最大活性为0.2 nM。相比之下，水蛭素-α-凝血酶和D-苯丙氨酰-L-丙基-L-丙氨酰氯甲基酮-α-凝血酶均缺乏酶活性，不能引起成纤维细胞收缩。因此，凝血酶的酶活性似乎是促进成纤维细胞收缩所必需的。北方分析证实，这些人成纤维细胞表达人α-凝血酶受体的mRNA。此外，代表活化α-凝血酶受体的“拴系配体”部分的合成肽（SFLLRNPND-KYEPF）促进成纤维细胞收缩，而前两个氨基酸被逆转的对照异构体肽未能引起这种反应。这些发现表明α-凝血酶促进成人成纤维细胞的收缩，并且人α-凝血酶受体的裂解足以产生这种反应。
Fibroblast contraction is proposed to play an important role in tissue contraction during events such as wound healing. Thrombin has been implicated to promote force generation in fibroblasts; however, its extracellular mode of action is unclear. The purpose of this study was to determine the role thrombin and the activation of its receptor plays in promoting the contraction of human fibroblasts in anin vitrocollagen lattice contraction assay. Human α-thrombin promoted fibroblast contraction in a dose-dependent manner with maximal activity at 0.2 nM. In contrast, both hirudin-α-thrombin and D-phenylalanyl-L-propyl-L-arginyl chloromethyl ketone-α-thrombin, which lack enzymatic activity, failed to elicit fibroblast contraction. Thus, the enzymatic activity of thrombin appears to be necessary for promotion of fibroblast contraction. Northern analysis confirmed that these human fibroblasts expressed mRNA for the human α-thrombin receptor. Moreover, the synthetic peptide (SFLLRNPND-KYEPF) representing the "tethered ligand" portion of the activated α-thrombin receptor promoted fibroblast contraction, while a control isomer peptide, in which the first two amino acids were reversed, failed to elicit this response. These findings indicate that α-thrombin promotes the contraction of adult human fibroblasts and that cleavage of the human α-thrombin receptor is sufficient to produce this response.