肾小管细胞外泌体miR-26a-5p靶向巨噬细胞FGF21促进肾小管间质炎症-东南大学学报医学版

肾小管细胞外泌体miR-26a-5p靶向巨噬细胞FGF21促进肾小管间质炎症

单位：1. 扬中市人民医院肾内科, 江苏扬中 212200;
2. 东南大学附属中大医院肾内科, 江苏南京 210009

关键词：肾小管间质炎症肾小管上皮细胞巨噬细胞 microRNA-26a-5p 成纤维细胞生长因子21 小鼠

分类号：R692.6

出版年·卷·期（页码）：2026·45·第一期（11-23）

摘要：

目的:探讨肾小管上皮细胞外泌体microRNA-26a-5p(miR-26a-5p)在调控巨噬细胞成纤维细胞生长因子21(FGF21)表达及其促进肾小管间质炎症中的作用机制。方法:采用单侧输尿管梗阻(UUO)模型和脂多糖(LPS)诱导脓毒症小鼠模型,通过外泌体分泌抑制、敲减miR-26a-5p及过表达FGF21等手段,结合逆转录实时荧光定量聚合酶链式反应(RT-qPCR)、Western blotting、免疫组化、免疫荧光及荧光素酶实验,研究外泌体miR-26a-5p在肾小管上皮细胞与巨噬细胞间的信号传递作用。结果:体内实验显示,抑制外泌体分泌或敲减miR-26a-5p均减轻肾小管间质炎症,过表达FGF21缓解肾小管间质炎症。体外实验显示,抑制肾小管上皮细胞外泌体分泌及外泌体miR-26a-5p表达、过表达巨噬细胞FGF21均减轻LPS诱导的巨噬细胞炎症;荧光素酶报告基因显示miR-26a-5p特异性结合FGF21 mRNA。结论:肾小管上皮细胞分泌外泌体miR-26a-5p,靶向抑制巨噬细胞FGF21表达,促进肾小管间质炎症。

Objective: To investigate the mechanism by which tubular epithelial cell-derived exosomal microRNA-26a-5p(miR-26a-5p) regulates macrophage fibroblast growth factor 21(FGF21) expression and promotes tubulointerstitial inflammation. Methods: Unilateral ureteral obstruction(UUO) and lipopolysaccharide(LPS)-induced sepsis mouse models were established. Exosome secretion inhibition,miR-26a-5p knockdown,and FGF21 overexpression were performed,combined with reverse transcription quantitative real-time PCR(RT-qPCR),Western blotting,immunohistochemistry,immunofluorescence,and luciferase reporter assays to elucidate the role of exosomal miR-26a-5p in signal transmission between renal tubular epithelial cells and macrophages. Results: In vivo,exosome release inhibition or miR-26a-5p knockdown alleviated tubulointerstitial inflammation,while FGF21 overexpression mitigated renal inflammatory injury. In vitro, suppression of exosome secretion and exosomal miR-26a-5p expression in tubular epithelial cells,as well as FGF21 overexpression in macrophages,attenuated LPS-induced macrophage inflammation. Dual-luciferase assays confirmed that miR-26a-5p directly targets FGF21 mRNA. Conclusion: Tubular epithelial cells transfer miR-26a-5p to macrophages via exosomes,where it suppresses FGF21 expression and promotes tubulointerstitial inflammation.

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