Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.
Department of Clinical Medicine, Xuzhou Medical University, Xuzhou 221004, China.
Cells. 2024 May 9;13(10):805. doi: 10.3390/cells13100805.
O-linked-β-D-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation), which is dynamically regulated by -GlcNAc transferase (OGT) and -GlcNAcase (OGA), is a post-translational modification involved in multiple cellular processes. O-GlcNAcylation of proteins can regulate their biological functions via crosstalk with other post-translational modifications, such as phosphorylation, ubiquitination, acetylation, and methylation. Liver diseases are a major cause of death worldwide; yet, key pathological features of the disease, such as inflammation, fibrosis, steatosis, and tumorigenesis, are not fully understood. The dysregulation of O-GlcNAcylation has been shown to be involved in some severe hepatic cellular stress, viral hepatitis, liver fibrosis, nonalcoholic fatty acid liver disease (NAFLD), malignant progression, and drug resistance of hepatocellular carcinoma (HCC) through multiple molecular signaling pathways. Here, we summarize the emerging link between O-GlcNAcylation and hepatic pathological processes and provide information about the development of therapeutic strategies for liver diseases.
O-连接-β-D-N-乙酰氨基葡萄糖（O-GlcNAc）糖基化（O-GlcNAcylation）是一种翻译后修饰，受β-N-乙酰氨基葡萄糖转移酶（OGT）和β-N-乙酰氨基葡萄糖苷酶（OGA）的动态调控，参与多种细胞过程。蛋白质的 O-GlcNAcylation 可以通过与其他翻译后修饰（如磷酸化、泛素化、乙酰化和甲基化）的相互作用来调节其生物学功能。肝脏疾病是全球主要的死亡原因之一；然而，该疾病的关键病理特征，如炎症、纤维化、脂肪变性和肿瘤发生，尚未完全了解。通过多种分子信号通路，已经表明 O-GlcNAcylation 的失调与某些严重的肝细胞应激、病毒性肝炎、肝纤维化、非酒精性脂肪性肝病（NAFLD）、恶性进展和肝细胞癌（HCC）的耐药性有关。在这里，我们总结了 O-GlcNAcylation 与肝脏病理过程之间的新联系，并提供了有关治疗肝脏疾病的治疗策略的发展信息。
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