Dong Qian, Xu Huan, Xu Pengjie, Liu Jiang, Shen Zhouji, Li Yabin
Department of Nephrology, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, China.
School of Life Sciences and Technology, Tongji University, Shanghai, China.
Front Immunol. 2025 Aug 15;16:1642446. doi: 10.3389/fimmu.2025.1642446. eCollection 2025.
Acute kidney injury (AKI) remains a life-threatening syndrome with elusive molecular drivers. Although ribosomal proteins such as RPL11 are increasingly recognized for their extra-ribosomal functions, their roles in AKI pathogenesis remain unexplored.
The comprehensive multi-omics analysis of mouse AKI kidneys combined scRNA-seq and RNA-seq to identify core regulatory factors. Based on cisplatin induced AKI, a HK-2 cell model was established by siRNA transfection silencing RPL11, while kidney targeted silencing was achieved using LyP-1 modified nanoparticles encapsulating si-RPL11. Technologies such as Western blotting, qPCR, and IVS fluorescence imaging ensure the successful construction of cell and animal models. Functional testing includes CCK-8, EdU assay, flow cytometry, TUNEL assay, qPCR, ELISA, and histopathological techniques to evaluate cell proliferation, apoptosis, and inflammatory cytokine levels.
RPL11 was identified as the core gene with AKI-specific upregulation in proximal tubules. RPL11 expression correlated with AKI severity and showed positive associations with Scr/KIM-1. The specific silencing of RPL11 in HK-2 cells was successfully induced and the LYS-1 peptide-modified cationic liposome nanoparticles were stable in quality and could target the renal tissue of AKI mice to silence RPL11. The experimental results have jointly confirmed that RPL11 suppressed proliferation, accelerated apoptosis, amplified inflammation and aggravated tubular necrosis and CD68 macrophage infiltration and .
RPL11 drives AKI progression by orchestrating tubular dysfunction, apoptosis, and immune dysregulation. Our renal-targeted nano-intervention validates RPL11 as a therapeutically actionable target, providing a novel strategy for biomarker-guided AKI management.
急性肾损伤（AKI）仍然是一种威胁生命的综合征，其分子驱动因素尚不明确。尽管核糖体蛋白如RPL11因其核糖体以外的功能而越来越受到认可，但其在AKI发病机制中的作用仍未得到探索。
对小鼠AKI肾脏进行全面的多组学分析，结合单细胞RNA测序（scRNA-seq）和RNA测序来确定核心调节因子。基于顺铂诱导的AKI，通过小干扰RNA（siRNA）转染沉默RPL11建立了HK-2细胞模型，同时使用包裹si-RPL11的LyP-1修饰纳米颗粒实现肾脏靶向沉默。蛋白质免疫印迹法、定量聚合酶链反应（qPCR）和活体荧光成像等技术确保了细胞和动物模型的成功构建。功能测试包括细胞计数试剂盒-8（CCK-8）、5-乙炔基-2'-脱氧尿苷（EdU）检测、流式细胞术、末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）检测、qPCR、酶联免疫吸附测定（ELISA）和组织病理学技术，以评估细胞增殖、凋亡和炎性细胞因子水平。
RPL11被确定为近端小管中AKI特异性上调的核心基因。RPL11表达与AKI严重程度相关，并与血肌酐/肾损伤分子-1（Scr/KIM-1）呈正相关。成功诱导HK-2细胞中RPL11的特异性沉默，且LYS-1肽修饰的阳离子脂质体纳米颗粒质量稳定，可靶向AKI小鼠的肾组织沉默RPL11。实验结果共同证实，RPL11抑制细胞增殖、加速细胞凋亡、放大炎症反应并加重肾小管坏死和CD68巨噬细胞浸润。
RPL11通过协调肾小管功能障碍、细胞凋亡和免疫失调来推动AKI进展。我们的肾脏靶向纳米干预验证了RPL11作为一个可用于治疗的靶点，为生物标志物引导的AKI管理提供了一种新策略。
