从口腔溃疡的信号传导和相关因子的角度对近期文献进行综述,为研究和治疗口腔溃疡提供理论参考。口腔溃疡的致病机制涉及诸多诱导因素和信号通路。外界的信号因子、机体的免疫因子、细胞表面的受体分子、细胞内的信号传递等众多因素,以及它们相关信号通路在口腔粘膜中的变化,在口腔溃疡的发展和愈合过程中发挥着不同的作用。本文从TGF-β、Smad7、FOXO1、TNF-α、IL-17、NO和ROS、JNK,以及靶向治疗药物和免疫检查点抑制剂等角度,对目前在口腔溃疡的致病及修复机制中相关因子和信号通路的研究进展进行了综述。它们之间的相互影响说明需要在炎症反应和组织修复之间达到平衡才能促进口腔溃疡愈合,例如ROS/NO经由PGE2加重炎症反应,还可经由JNK/TGF-β途径促进细胞增殖和迁移以进行修复;TNF-α除了促进T细胞产生各种炎症因子,还经由JNK/c-Jun途径促进胶原和MMPs合成以帮助组织修复;Smad7和IL-17则参与抑制炎症反应和促进细胞分泌抗菌物质。因而平衡免疫系统可能是未来口腔溃疡药物的研究方向。
The recent literature has been reviewed from the signal transduction and related factors of oral ulcers to provide theoretical reference for the research and treatment thereof. The pathogenic mechanism of oral ulcers is complex, involving immune abnormalities, trauma, excessive fatigue, hormone changes, vitamin deficiency, genetic factors, etc. Common manifestations include oral candidiasis, recurrent aphthous ulcers, or cancer patients with radiation or drug treatment, which have resulted in mucosal ulcers that greatly affect the life quality of patients. The pathogenic mechanism of oral ulcers involves many inducing factors and signal pathways. The composition and content of factors, such as external signal factors, immune factors of the body, receptor molecules on the cell surface, and intracellular signal transmission, as well as the changes in their related signal pathways, have played different roles in the development and healing process of oral ulcers. In this review, NF-κB and TNF-α have been discussed a lot. This review combines recent reports in the literature, from the aspects of TGF-β, Smad7, FOXO1, TNF-α, IL-17, NO and ROS, JNK, targeted therapy drugs, immune checkpoint inhibitors, etc. Thus the current research progress of related factors and signal pathways in causes and repair mechanisms of oral ulcers has been reviewed. IL-6, IL-8, COX-2, TLRs, Dectine-1, p38 MAPK, etc. are interspersed in relevant introductions. By analyzing the possible connections between them, it is found that a balance between inflammation and tissue repair is needed to promote oral ulcer healing. For example, ROS/NO aggravates inflammation through PGE2, but it promotes cell proliferation and migration through JNK/TGF-β pathway for repair. TNF-α promotes the production of various inflammatory factors by T cells, and yet it promotes the synthesis of collagen and MMPs through the JNK/c-Jun pathway to help tissue repair. Smad7 and IL-17 are involved in inhibiting inflammation and promoting cell secretion of antibacterial substances. Targeted therapies or immune checkpoint inhibitors that act on a single target mostly cause oral inflammation in patients to varying degrees. Therefore, balancing the immune system may be the future direction of research for oral ulcer drugs.
