Previous in vivo and in vitro studies have shown that Akt1 serves as a crucial regulator of vascular maturation, extracellular matrix composition, and angiogenesis in tumors. Hence, we hypothesized that Akt1 may be necessary for other angiogenesis-dependent processes, including wound healing. Using Akt1 (-/-) and Akt2 (-/-) mice, we demonstrate that deficiency of Akt1, but not Akt2, results in impaired assembly of collagen in skin wounds and around the blood vessels. Wounds in Akt1 (-/-) mice, but not in Akt2 (-/-) mice, were characterized by reduced vascular area as well as impaired vascular maturation as evidenced by reduced smooth muscle cell recruitment. Expression level of a major angiogenic growth factor, VEGF, was significantly lower in wound tissues of Akt1 (-/-) mice as compared to WT. However, despite the impaired collagen assembly and reduced angiogenesis in Akt1 (-/-) wounds, no significant difference in migration of fibroblasts into the wound area was observed between WT and Akt1 (-/-) mice. Importantly, the dynamics of wound closure were similar between WT, Akt1 (-/-), and Akt2 (-/-) mice. Thus, it appears that although the lack of Akt1 impairs VEGF expression, wound angiogenesis, and subsequent maturation of vasculature, it has no effect on the wound closure. These findings may have clinical applications for the improvement of treatment procedures with reported history of wound healing complications.

译文

先前的体内和体外研究表明,Akt1是肿瘤中血管成熟,细胞外基质组成和血管生成的关键调节剂。因此,我们假设Akt1可能是其他血管生成依赖性过程 (包括伤口愈合) 所必需的。使用Akt1 (-/-) 和Akt2 (-/-) 小鼠,我们证明Akt1的缺乏而不是Akt2的缺乏会导致皮肤伤口和血管周围胶原蛋白的组装受损。Akt1 (-/-) 小鼠的伤口,但Akt2 (-/-) 小鼠的伤口的特征是血管面积减少以及血管成熟受损,平滑肌细胞募集减少证明了这一点。与WT相比,Akt1 (-/-) 小鼠伤口组织中主要血管生成生长因子VEGF的表达水平显着降低。然而,尽管在Akt1 (-/-) 伤口中胶原蛋白组装受损且血管生成减少,但在WT和Akt1 (-/-) 小鼠之间未观察到成纤维细胞向伤口区域迁移的显着差异。重要的是,WT,Akt1 (-/-) 和Akt2 (-/-) 小鼠之间的伤口闭合动力学相似。因此,尽管缺乏Akt1会损害VEGF的表达,伤口血管生成以及随后的脉管系统成熟,但它对伤口闭合没有影响。这些发现可能具有临床应用,可用于改善伤口愈合并发症史的治疗程序。

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