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中华肾病研究电子杂志 ›› 2025, Vol. 14 ›› Issue (04) : 209 -213. doi: 10.3877/cma.j.issn.2095-3216.2025.04.005

综述

哺乳动物雷帕霉素靶蛋白信号通路在IgA肾病发病机制中的作用研究进展
王辉1,2,(), 崔恬玉1,2, 段凡2   
  1. 1071000 首都医科大学附属北京儿童医院保定医院肾脏内科,国家儿童区域医疗中心,保定市儿童肾脏病基础与临床重点实验室
    2100045 国家儿童医学中心、首都医科大学附属北京儿童医院
  • 收稿日期:2025-03-21 出版日期:2025-08-28
  • 通信作者: 王辉
  • 基金资助:
    保定市科技计划项目(2211ZF001); 河北省中医药类科学研究课题计划项目(2025145)

Progress in the study of the role of the mammalian target of rapamycin signaling pathway in the pathogenesis of IgA nephropathy

Hui Wang1,2,(), Tianyu Cui1,2, Fan Duan2   

  1. 1Department of Nephrology, Baoding Hospital of Beijing Children′s Hospital Affiliated to Capital Medical University, National Children′s Regional Medical Center, Baoding Key Laboratory of Basic and Clinical Pediatric Nephrology, Baoding 071000, Hebei Province
    2Beijing Children′s Hospital Affiliated to Capital Medical University, National Center for Children′s Health, Beijing 100045; China
  • Received:2025-03-21 Published:2025-08-28
  • Corresponding author: Hui Wang
引用本文:

王辉, 崔恬玉, 段凡. 哺乳动物雷帕霉素靶蛋白信号通路在IgA肾病发病机制中的作用研究进展[J/OL]. 中华肾病研究电子杂志, 2025, 14(04): 209-213.

Hui Wang, Tianyu Cui, Fan Duan. Progress in the study of the role of the mammalian target of rapamycin signaling pathway in the pathogenesis of IgA nephropathy[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2025, 14(04): 209-213.

IgA肾病是一种以半乳糖缺乏型IgA1在肾小球沉积为特点的自身免疫性肾病,其发病机制主要为"多重打击学说",包括黏膜免疫异常、免疫复合物形成、补体激活及肾脏纤维化。近年研究发现,在IgA肾病的发病机制中,被过度激活的哺乳动物雷帕霉素靶蛋白信号通路,能够促进系膜细胞增殖、抑制自噬、加剧纤维化,从而促进疾病进展。本文综述了哺乳动物雷帕霉素靶蛋白信号通路在IgA肾病发病机制中的作用研究进展,并探讨了其作为治疗IgA肾病靶点的潜力。

IgA nephropathy is an autoimmune kidney disease characterized by glomerular deposition of galactose-deficient IgA1. Its pathogenesis is primarily attributed to the "multi-hit hypothesis", encompassing mucosal immune abnormalities, formation of immune complexes, complement activation, and renal fibrosis. Recent studies have demonstrated that in the pathogenesis of IgA nephropathy, hyperactivation of the mammalian target of rapamycin (mTOR) signaling pathway could promote mesangial cell proliferation, suppressing autophagy, and exacerbating fibrosis. This article reviewed the progress in the study of the role of mTOR signaling pathway in the pathogenesis of IgA nephropathy, and explored its potential as a therapeutic target of IgA nephropathy.

图1 哺乳动物雷帕霉素靶蛋白在IgA肾病"多重打击学说"中的作用注:A:IgA肾病中,感染、食物抗原、微生物群的作用下,异常的粘膜免疫反应促进B细胞表达Gd-IgA1,粘膜来源的Gd-IgA1阳性B细胞被错误地运送到骨髓中,或者是从粘膜部位过量的Gd-IgA1进入血液循环,均导致IgAN患者血液中Gd-IgA1水平升高(四重打击①)。B:在血液循环中,Gd-IgA1被IgG和IgA1特异性的Gd-IgA1铰链区抗体识别,这些抗体可能是自身抗体或交叉反应性抗菌抗体,这种识别导致含有Gd-IgA1的致病性免疫复合物形成(四重打击②)。C:在肾脏中,含有Gd-IgA1的致病性免疫复合物沉积在肾小球系膜内(四重打击③),导致系膜细胞活化、增殖、炎症介质和细胞外基质成分的产生以及补体活化(四重打击④)。造成肾小球和小管间质损伤
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