B-Cell Epigenetic Modulation of IgA Response by 5-Azacytidine and IgA Nephropathy.

IF 10.3 1区医学 Q1 UROLOGY & NEPHROLOGY

Journal of The American Society of Nephrology Pub Date : 2024-08-13 DOI:10.1681/ASN.0000000000000441

Shanshan Yu, Xiang Li, Ting Wang, Jingyi Li, Hongzhi Li, Ying Xu, Yanling Hu, Fubin Zhu, Jinwei Wang, Tianhe Wang, Bin Zhu, Xu-Jie Zhou, Hong Zhang, Jicheng Lv, Jonathan Barratt, Binghai Zhao

引用次数: 0

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5-Azacytidine 和 IgA 肾病对 IgA 反应的 B 细胞表观遗传调控

背景：IgA肾病是全球肾衰竭的重要原因之一。IgA生成失调被认为在IgA肾病发病机制中起着关键作用，然而，人们对RNA 5-甲基胞嘧啶（5mC）修饰等表观遗传学机制在调控IgA合成中的作用知之甚少：为了破译 RNA 5mC 在调控 IgA 类别转换中的作用，用 5-azacytidine 处理 miR-23b-/- 和 LCWE 诱导的川崎病小鼠。我们还采用了 Trdmt1-/- 和双 Trdmt1-/-/ miR-23b-/- 小鼠、Aid-/- 小鼠或 Aid-/-/ miR-23b-/- 小鼠：结果：我们发现，miR-23b能下调转移RNA天冬氨酸甲基转移酶1（Trdmt1）的表达，从而减少5-甲基胞嘧啶（m5C）RNA修饰和B细胞中IgA的合成。抑制 m5C RNA 修饰可使 miR-23b-/- 和川崎病小鼠的血清 IgA 水平恢复正常，并改善 IgA 肾病样肾病的进展，而 Trdmt1-/-miR-23b-/- 小鼠的系膜 IgA 和 C3 沉积则不会发展。miR-23b 对血清 IgA 水平的调控以及 miR-23b-/- 和川崎病小鼠 IgA 肾病样肾病的发生可能是通过 TRDMT1 驱动 B 细胞中的 5-甲基胞嘧啶 RNA 修饰，导致活化诱导的胞苷脱氨酶活性受损和 IgA 类开关重组介导的：这项研究揭示了TRDMT1诱导的RNA 5mC甲基化调控IgA类开关，而5-氮杂胞嘧啶抑制RNA 5mC可改善IgA肾病的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of The American Society of Nephrology 医学-泌尿学与肾脏学

CiteScore

22.40

自引率

2.90%

发文量

492

审稿时长

3-8 weeks

期刊介绍： The Journal of the American Society of Nephrology (JASN) stands as the preeminent kidney journal globally, offering an exceptional synthesis of cutting-edge basic research, clinical epidemiology, meta-analysis, and relevant editorial content. Representing a comprehensive resource, JASN encompasses clinical research, editorials distilling key findings, perspectives, and timely reviews. Editorials are skillfully crafted to elucidate the essential insights of the parent article, while JASN actively encourages the submission of Letters to the Editor discussing recently published articles. The reviews featured in JASN are consistently erudite and comprehensive, providing thorough coverage of respective fields. Since its inception in July 1990, JASN has been a monthly publication. JASN publishes original research reports and editorial content across a spectrum of basic and clinical science relevant to the broad discipline of nephrology. Topics covered include renal cell biology, developmental biology of the kidney, genetics of kidney disease, cell and transport physiology, hemodynamics and vascular regulation, mechanisms of blood pressure regulation, renal immunology, kidney pathology, pathophysiology of kidney diseases, nephrolithiasis, clinical nephrology (including dialysis and transplantation), and hypertension. Furthermore, articles addressing healthcare policy and care delivery issues relevant to nephrology are warmly welcomed.