Takeda Hikaru, Katagata Yohtaro, Hozumi Yutaka, Kondo Shigeo
Department of Dermatology, Yamagata University, School of Medicine, 2-2-2, Iida-Nishi, Yamagata 990-9585, Japan.
Am J Pathol. 2004 Nov;165(5):1653-62. doi: 10.1016/S0002-9440(10)63422-0.
The tissue angiotensin (Ang) system, which acts independently of the circulating renin Ang system, is supposed to play an important role in tissue repair in the heart and kidney. In the skin, the role of the system for wound healing has remained to be ascertained. Our study demonstrated that oral administration of selective AngII type-1 receptor (AT(1)) blocker suppressed keratinocyte re-epithelization and angiogenesis during skin wound healing in rats. Immunoprecipitation and Western blot analysis indicated the existence of AT(1) and AngII type-2 receptor (AT(2)) in cultured keratinocytes and myofibroblasts. In a bromodeoxyuridine incorporation study, induction of AT(1) signaling enhanced the incorporation into keratinocytes and myofibroblasts. Wound healing migration assays revealed that induction of AT(1) signaling accelerated keratinocyte re-epithelization and myofibroblasts recovering. In these experiments, induction of AT(2) signaling acted vice versa. Taken together, our study suggests that skin wound healing is regulated by balance of opposing signals between AT(1) and AT(2).
组织血管紧张素(Ang)系统独立于循环肾素血管紧张素系统发挥作用,被认为在心脏和肾脏的组织修复中起重要作用。在皮肤中,该系统对伤口愈合的作用尚待确定。我们的研究表明,口服选择性血管紧张素II 1型受体(AT(1))阻滞剂可抑制大鼠皮肤伤口愈合过程中的角质形成细胞再上皮化和血管生成。免疫沉淀和蛋白质印迹分析表明,在培养的角质形成细胞和成肌纤维细胞中存在AT(1)和血管紧张素II 2型受体(AT(2))。在一项溴脱氧尿苷掺入研究中,AT(1)信号的诱导增强了其向角质形成细胞和成肌纤维细胞中的掺入。伤口愈合迁移试验表明,AT(1)信号的诱导加速了角质形成细胞再上皮化和成肌纤维细胞的恢复。在这些实验中,AT(2)信号的诱导则起相反作用。综上所述,我们的研究表明,皮肤伤口愈合受AT(1)和AT(2)之间相反信号平衡的调节。