Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, China.
Department of Clinical Laboratory, Xijing Hospital, The Fourth Military Medical University, China.
Arch Biochem Biophys. 2020 Mar 30;682:108286. doi: 10.1016/j.abb.2020.108286. Epub 2020 Jan 30.
Pathological scar is a common complication after wound healing. One of the most important factors that affects scar formation is inflammation. During this process, macrophages play a critical role in the wound healing process, as well as in scar formation. Notch signaling is reported to participate in inflammation and fibrosis; however, whether it affects scar formation is still unclear. In this study, RBP-J knockout mice, in which Notch signaling was down-regulated, and control mice were used, and a skin incision model was established. Sirius red staining and Masson staining suggested that RBP-J knockout could significantly reduce collagen sedimentation after wound healing. Western blot analysis and RT-PCR also confirmed the results. During wound healing, the expression of inflammatory cytokines and macrophage infiltration were decreased in RBP-J knockout mice. In vitro, it was also verified that RBP-J deficiency in macrophages effectively suppressed the expression of inflammatory cytokines and chemotaxis of macrophages after LPS stimulation. In conclusion, blocking Notch signaling in macrophages effectively alleviated scar formation by suppressing the inflammatory response and collagen sedimentation.
病理性瘢痕是创伤愈合后的常见并发症。影响瘢痕形成的最重要因素之一是炎症。在这个过程中，巨噬细胞在伤口愈合过程中以及瘢痕形成中起着关键作用。有报道称 Notch 信号参与炎症和纤维化；然而，它是否影响瘢痕形成尚不清楚。在这项研究中，使用了 Notch 信号下调的 RBP-J 敲除小鼠和对照小鼠，并建立了皮肤切口模型。天狼星红染色和 Masson 染色表明，RBP-J 敲除可显著减少伤口愈合后胶原沉积。Western blot 分析和 RT-PCR 也证实了这一结果。在伤口愈合过程中，RBP-J 敲除小鼠的炎症细胞因子表达和巨噬细胞浸润减少。体外实验还证实，巨噬细胞中 RBP-J 的缺失可有效抑制 LPS 刺激后炎症细胞因子的表达和巨噬细胞的趋化性。总之，阻断巨噬细胞中的 Notch 信号通过抑制炎症反应和胶原沉积，有效缓解了瘢痕形成。
