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  3. Brain-derived extracellular vesicles circUsp32 polarized macrophages causing acute kidney injury after traumatic brain injury

Brain-derived extracellular vesicles circUsp32 polarized macrophages causing acute kidney injury after traumatic brain injury

  • Sci Adv. 2025 Nov 28;11(48):eadz1243. doi: 10.1126/sciadv.adz1243.
Jiayuanyuan Fu 1,  Jingheng Wu 1,  Mengran Du 2,  Xu Wang 1,  Qi Shi 1,  Yehong Fang 1,  Yu Lan 1,  Qiaoli Wu 1 3,  Guobin Zhang 1 3,  Lixia Xu 1 3,  Hua Yan 1 3
Affiliations

Affiliations

  • 1 Huanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin 300070, China.
  • 2 Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing 400016, China.
  • 3 Tianjin Key Laboratory of Cerebral Blood Flow Reconstruction and Head and Neck Tumor New Technology Translation, Tianjin Huanhu Hospital, Tianjin 300350, China.
PMID: 41296848 DOI: 10.1126/sciadv.adz1243
Abstract

Brain-kidney cross-talk following traumatic brain injury (TBI) can induce acute kidney injury (AKI), but mechanisms remain unclear. Extracellular vesicles derived from injured brain tissue (TBI-EVs) may mediate brain-kidney interactions. In vivo experiments demonstrated that TBI-EVs causes AKI by promoting pro-inflammatory macrophage polarization. TBI-EVs markedly increased AKI markers and proportion of pro-inflammatory-polarized macrophages. Mechanistically, transcriptomics of TBI-EVs revealed high circUsp32 expression. Subsequent in vitro assays showed that circUsp32 competitively binds to the SH2 domain of suppressor of cytokine signaling 1 (Socs1), affecting interferon regulator factor 7 (IRF7) ubiquitination and promoting pro-inflammatory polarization. CircUsp32 knockdown reduced pro-inflammatory polarization and alleviated AKI in TBI mice. In addition, circUsp32 is homologous to hsa_circ_0044940, which may serve as a predicted biomarker of AKI after TBI. Notably, AKI following TBI may contribute to neuroinflammation via uremic toxins. Collectively, these findings suggest that circUsp32 mediates macrophage polarization through the Socs1/IRF7 axis and could be a potential biomarker for AKI following TBI.

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