Abstract：
Dermal fibroblasts are essential cells of skin tissue responsible for its normal functioning. In skin wounds, the differentiation of resident fibroblasts into myofibroblasts occurs, which is accompanied by the rearrangement of actin cytoskeleton with the expression of alpha-smooth muscle actin. This transformation is a prerequisite for a successful wound healing. At the same time, different studies indicate that extracellular matrix may be involved in regulation of this process. Since the connection between cells and matrix is provided by transmembrane integrin receptors, this work was aimed at studying the dynamics of signaling pathways associated with integrins on an in vitro model of wound healing using human skin fibroblasts. It was shown that the healing of simulated wound was accompanied by a change in the level of integrins as well as integrin-associated kinases ILK (integrin-linked kinase) and FAK (focal adhesion kinase). Pharmacological inhibition of ILK and FAK caused the suppression of p38 and Akt which proteins are involved in regulation of the actin cytoskeleton. Moreover, it resulted in an inefficient wound closure in vitro. The results of this study support the involvement of integrin-associated kinases in regulation of fibroblast-to-myofibroblast transition during wound healing.
摘要：
真皮成纤维细胞是负责其正常功能的皮肤组织的必需细胞。在皮肤伤口，常驻成纤维细胞分化为肌成纤维细胞，伴随着肌动蛋白细胞骨架的重排和α-平滑肌肌动蛋白的表达。这种转变是成功伤口愈合的先决条件。同时,不同的研究表明，细胞外基质可能参与了这一过程的调节。由于细胞和基质之间的连接是由跨膜整合素受体提供的，这项工作旨在研究使用人皮肤成纤维细胞在伤口愈合的体外模型上与整合素相关的信号通路的动力学。结果表明，模拟伤口的愈合伴随着整合素以及整合素相关激酶ILK（整合素连接激酶）和FAK（粘着斑激酶）水平的变化。ILK和FAK的药理学抑制引起p38和Akt的抑制,p38和Akt蛋白参与肌动蛋白细胞骨架的调节。此外，它导致在体外无效的伤口闭合。这项研究的结果支持整合素相关激酶在伤口愈合过程中参与成纤维细胞到肌成纤维细胞的转变的调节。
