Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, Sapienza University of Rome, 00185 Rome, Italy.
Int J Mol Sci. 2019 Aug 20;20(16):4061. doi: 10.3390/ijms20164061.
One of the main mechanisms carried out by the cells to counteract several forms of stress is the activation of the nuclear factor erythroid 2-related factor (Nrf2) signaling. Nrf2 signaling controls the expression of many genes through the binding of a specific -acting element known as the antioxidant response element (ARE). Activation of Nrf2/ARE signaling can mitigate several pathologic mechanisms associated with an autoimmune response, digestive and metabolic disorders, as well as respiratory, cardiovascular, and neurodegenerative diseases. Indeed, several studies have demonstrated that Nrf2 pathway plays a key role in inflammation and in cancer development in many organs, including the intestine. Nrf2 appears to be involved in inflammatory bowel disease (IBD), an immune-mediated chronic and disabling disease, with a high risk of developing intestinal fibrotic strictures and cancer. Currently, drugs able to increase cytoprotective Nrf2 function are in clinical trials or already being used in clinical practice to reduce the progression of some degenerative conditions. The role of Nrf2 in cancer development and progression is controversial, and drugs able to inhibit abnormal levels of Nrf2 are also under investigation. The goal of this review is to analyze and discuss Nrf2-dependent signals in the initiation and progression of intestinal fibrosis and cancers occurring in IBD.
细胞对抗多种形式应激的主要机制之一是激活核因子红细胞 2 相关因子 (Nrf2) 信号通路。Nrf2 信号通路通过结合特定的作用元件（称为抗氧化反应元件 (ARE)）来控制许多基因的表达。Nrf2/ARE 信号通路的激活可以减轻与自身免疫反应、消化和代谢紊乱以及呼吸、心血管和神经退行性疾病相关的几种病理机制。事实上，多项研究表明，Nrf2 通路在包括肠道在内的许多器官的炎症和癌症发展中起着关键作用。Nrf2 似乎与炎症性肠病 (IBD) 有关，IBD 是一种免疫介导的慢性和致残性疾病，有发展为肠道纤维性狭窄和癌症的高风险。目前，能够增加细胞保护性 Nrf2 功能的药物正在临床试验中，或已经在临床实践中用于减少一些退行性疾病的进展。Nrf2 在癌症发展和进展中的作用存在争议，能够抑制异常水平的 Nrf2 的药物也在研究中。本综述的目的是分析和讨论 Nrf2 依赖性信号在 IBD 中发生的肠道纤维化和癌症的起始和进展中的作用。
