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<p>Exosomes are extracellular vesicles involved in mediating cell–cell communication by shuttling genetic information and proteins. Here, we investigated whether glomerular endothelial cells-derived exosomes play a central role in mediating podocyte injury and proteinuria formation in diabetic kidney disease and its precise mechanism. In vitro, upon stimulation with high glucose and transforming growth factor-β1, primary human renal glomerular endothelial cells (HRGECs) produced more exosomes that directly mediated podocyte injury. Conversely, pharmacological inhibition of exosome secretion by GW4869, knockdown of tripartite motif-containing 27 (TRIM27) expression, or inhibition of miR-486-5p all abolished the ability of high glucose and transforming growth factor-β1-treated HRGECs to induce podocyte injury. In vivo, injections of HRGEC-derived exosomes aggravated podocyte injury and proteinuria in diabetic mice, which was negated by a miR-486-5p inhibitor. Furthermore, specific knockdown of TRIM27 expression or miR-486-5p in endothelial cells preserved kidney function and attenuated podocyte injury in diabetic mice. Thus, our results suggest that TRIM27-induced glomerular endothelial cell-derived exosomes play a major role in podocyte injury by shuttling miR-486-5p in diabetic kidney disease. Hence, strategies targeting exosomes may be a new direction in developing therapeutics for podocyte injury and proteinuria in diabetic kidney disease.</p><p></p>

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TRIM27-controlled endothelium-derived exosomes play a central role in podocyte injury in diabetic kidney disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月7日

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  • Yuexin Tian,
  • Yunhe Liu,
  • Xiaojuan Feng,
  • Lunbi Wu,
  • Weiwei Song,
  • Tongyu Zhao,
  • Jinxi Liu,
  • Xinyan Miao,
  • Haimin Ma,
  • Baiyun Jia,
  • Lihua Kang,
  • Qingjuan Liu,
  • Wei Zhang,
  • Huifang Guo,
  • Lin Yang,
  • Jinsheng Xu,
  • Shuxia Liu

摘要

Exosomes are extracellular vesicles involved in mediating cell–cell communication by shuttling genetic information and proteins. Here, we investigated whether glomerular endothelial cells-derived exosomes play a central role in mediating podocyte injury and proteinuria formation in diabetic kidney disease and its precise mechanism. In vitro, upon stimulation with high glucose and transforming growth factor-β1, primary human renal glomerular endothelial cells (HRGECs) produced more exosomes that directly mediated podocyte injury. Conversely, pharmacological inhibition of exosome secretion by GW4869, knockdown of tripartite motif-containing 27 (TRIM27) expression, or inhibition of miR-486-5p all abolished the ability of high glucose and transforming growth factor-β1-treated HRGECs to induce podocyte injury. In vivo, injections of HRGEC-derived exosomes aggravated podocyte injury and proteinuria in diabetic mice, which was negated by a miR-486-5p inhibitor. Furthermore, specific knockdown of TRIM27 expression or miR-486-5p in endothelial cells preserved kidney function and attenuated podocyte injury in diabetic mice. Thus, our results suggest that TRIM27-induced glomerular endothelial cell-derived exosomes play a major role in podocyte injury by shuttling miR-486-5p in diabetic kidney disease. Hence, strategies targeting exosomes may be a new direction in developing therapeutics for podocyte injury and proteinuria in diabetic kidney disease.