Liao Ziwei, Wang Jing, Xu Mengrou, Li Xiaoyan, Xu Hongming
Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Cell Dev Biol. 2024 Aug 16;12:1447135. doi: 10.3389/fcell.2024.1447135. eCollection 2024.
ALKBH5 is one of the demethylases involved in the regulation of RNA m6A modification. In addition to its role in the dynamic regulation of RNA m6A modification, ALKBH5 has been found to play important roles in various tissues fibrosis processes in recent years. However, the mechanisms and effects of ALKBH5 in fibrosis have been reported inconsistently. Multiple cell types, including parenchymal cells, immune cells (neutrophils and T cells), macrophages, endothelial cells, and fibroblasts, play roles in various stages of fibrosis. Therefore, this review analyzes the mechanisms by which ALKBH5 regulates these cells, its impact on their functions, and the outcomes of fibrosis. Furthermore, this review summarizes the role of ALKBH5 in fibrotic diseases such as pulmonary fibrosis, liver fibrosis, cardiac fibrosis, and renal fibrosis, and discusses various ALKBH5 inhibitors that have been discovered to date, exploring the potential of ALKBH5 as a clinical target for fibrosis.
ALKBH5是参与RNA m6A修饰调控的去甲基化酶之一。除了在RNA m6A修饰的动态调控中发挥作用外，近年来还发现ALKBH5在各种组织纤维化过程中起重要作用。然而，关于ALKBH5在纤维化中的机制和作用，报道并不一致。多种细胞类型，包括实质细胞、免疫细胞（中性粒细胞和T细胞）、巨噬细胞、内皮细胞和成纤维细胞，在纤维化的各个阶段发挥作用。因此，本综述分析了ALKBH5调节这些细胞的机制、其对细胞功能的影响以及纤维化的结局。此外，本综述总结了ALKBH5在肺纤维化、肝纤维化、心脏纤维化和肾纤维化等纤维化疾病中的作用，并讨论了迄今为止发现的各种ALKBH5抑制剂，探讨了ALKBH5作为纤维化临床靶点的潜力。
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