PRMT1及其底物：肾脏和代谢疾病中的新功能
PRMT1 and its Substrates: Novel functions in kidney and metabolic diseases.
摘要(中文译文)
蛋白精氨酸甲基转移酶1（PRMT1）最为人所知的是作为一种核表观遗传写入器，催化沉积激活性H4R3me2a标记。然而，PRMT1还可甲基化多种非组蛋白底物，分布于多个细胞区室。本综述超越以染色质为中心的模式，提供了一种以底物驱动的机制框架，用于理解其在肾脏疾病和代谢疾病中的作用。我们分析了四条已验证的底物轴：糖异生中的FoxO1、纤维化中的BRD4、脂肪酸代谢中的UBE2m以及炎症中的RelA。这些实例阐明了PRMT1如何以细胞类型特异性方式整合代谢、炎症和纤维化信号。一个关键见解是功能性多效性：PRMT1发挥相反的作用——在白色脂肪组织中抑制脂解，而在棕色脂肪中促进产热；在肾小管中抑制NF-κB，而在肝脏中促进促炎性巨噬细胞极化。这种复杂性挑战了将PRMT1视为统一促致病因素的观点。我们批判性评估了抑制剂研发格局，包括已终止的GSK3368715临床试验，并指出了主要的转化障碍。我们得出结论：要在慢性肾脏病和代谢疾病中实现治疗潜力，需要从广泛抑制转向情境选择性调控——通过底物选择性抑制剂、组织特异性递送和生物标志物指导的策略。
Abstract
Protein arginine methyltransferase 1 (PRMT1) is best known as a nuclear epigenetic writer that deposits the activating H4R3me2a mark. However, PRMT1 also methylates diverse non‑histone substrates across multiple cellular compartments, and this review moves beyond chromatin‑centric models to provide a substrate‑driven mechanistic framework in kidney and metabolic diseases. We analyze four validated substrate axes: FoxO1 in gluconeogenesis, BRD4 in fibrosis, UBE2m in fatty acid metabolism, and RelA in inflammation. These examples illustrate how PRMT1 integrates metabolic, inflammatory and fibrotic signals in a cell‑type‑specific manner. A key insight is functional pleiotropy: PRMT1 exerts opposing roles-restraining lipolysis in white adipose tissue while enabling thermogenesis in brown fat, and suppressing NF‑κB in renal tubules while promoting pro‑inflammatory macrophage polarization in the liver. This complexity challenges the view of PRMT1 as uniformly pro‑pathogenic. We critically evaluate the inhibitor landscape, including the terminated clinical trial of GSK3368715, and identify major translational barriers. We conclude that realizing therapeutic potential in chronic kidney and metabolic diseases requires a shift from broad inhibition toward context‑selective modulation-through substrate‑selective inhibitors, tissue‑specific delivery and biomarker‑guided strategies.
如何引用
AMA
Yu Zhu, Berthold Hocher, Fanna Liu. PRMT1 and its Substrates: Novel functions in kidney and metabolic diseases.. Diabetes research and clinical practice. 2026; doi:10.1016/j.diabres.2026.113278.
APA
Yu Zhu, Berthold Hocher, Fanna Liu (2026). PRMT1 and its Substrates: Novel functions in kidney and metabolic diseases.. Diabetes research and clinical practice. https://doi.org/10.1016/j.diabres.2026.113278
GB/T 7714
Yu Zhu, Berthold Hocher, Fanna Liu. PRMT1 and its Substrates: Novel functions in kidney and metabolic diseases.[J]. Diabetes research and clinical practice, 2026 doi:10.1016/j.diabres.2026.113278.
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