Dai Xiaoniu, Cheng Yusi, Luo Wei, Wang Jing, Wang Cuifen, Zhang Xinxin, Zhang Wei, Chao Jie
Jiangsu Provincial Key Laboratory of Critical Care Medicine Department of Physiology, School of Medicine Zhongda Hospital Southeast University 87 Dingjiaqiao Rd Nanjing Jiangsu 210009 China.
Tissue Sciences Facility University of Nebraska Medical Center 985815 Nebraska Medical Center Omaha NE6B19B-5815 USA.
Small Sci. 2024 Nov 21;5(2):2400308. doi: 10.1002/smsc.202400308. eCollection 2025 Feb.
Fibrosis is a pathological process characterized by the excessive deposition of extracellular matrix in the tissue's extracellular space, leading to structural injury and organ dysfunction, and even organ failure, posing a threat to human life. Despite mounting evidence suggesting that fibrosis is reversible, effective treatments for fibrotic diseases are lacking. Accumulating evidence has elucidated that ribonucleic acid (RNA) modifications have emerged as novel mechanisms regulating gene expression. N6-methyladenosine (m6A) modification is a well-known prevalent RNA posttranscriptional modification that participates in essential biological processes such as RNA splicing, translation, and degradation. It is tightly implicated in a wide range of cellular processes and various human diseases, particularly in organ fibrosis. The m6A modification is a dynamic and reversible process regulated by methylases, commonly known as "writers," and demethylases referred to as "erasers," while m6A modifications are recognized by "readers." Accumulating evidence suggests that m6A modification on RNAs is tightly associated with fibrotic diseases of visceral organs including the lungs, heart, liver, and kidney. In this review, recent advances in the impact of m6A methylation of RNAs on visceral organ fibrosis are highlighted and the potential prospects for therapy in treating fibrotic diseases of visceral organs are discussed.
纤维化是一种病理过程,其特征在于细胞外基质在组织的细胞外空间过度沉积,导致结构损伤和器官功能障碍,甚至器官衰竭,对人类生命构成威胁。尽管越来越多的证据表明纤维化是可逆的,但仍缺乏针对纤维化疾病的有效治疗方法。越来越多的证据表明,核糖核酸(RNA)修饰已成为调节基因表达的新机制。N6-甲基腺苷(m6A)修饰是一种众所周知的普遍存在的RNA转录后修饰,参与RNA剪接、翻译和降解等重要生物学过程。它与广泛的细胞过程和各种人类疾病密切相关,尤其是器官纤维化。m6A修饰是一个由甲基化酶(通常称为“书写器”)和去甲基化酶(称为“擦除器”)调节的动态可逆过程,而m6A修饰则由“读取器”识别。越来越多的证据表明,RNA上的m6A修饰与包括肺、心脏、肝脏和肾脏在内的内脏器官的纤维化疾病密切相关。在这篇综述中,重点介绍了RNA的m6A甲基化对内脏器官纤维化影响的最新进展,并讨论了治疗内脏器官纤维化疾病的潜在前景。
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