ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Sympathetic Activation Promotes Kidney Fibrosis in Mice via Macrophage-Derived N2ICD-Enriched Extracellular Vesicles.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- The dual role of exosomes in renal fibrosis and their potential for clinical translational applications.Renal failure · 2026Review
- Macrophage-Fibroblast Crosstalk in Kidney Injury: A Narrative Review.International journal of molecular sciences · 2026Review
- Neural regulation of cancer: from microenvironmental hijacking to systemic circuit co-option.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Kidney-heart crosstalk: the extracellular vesicles connection.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Review
- Review
- The Lung-Kidney Axis: A Coordinated Regulation of Oxygen Sensing and Erythropoiesis.Biomedicines · 2026Review
- Sympathetic Activation Promotes Kidney Fibrosis in Mice via Macrophage-Derived N2ICD-Enriched Extracellular Vesicles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Persistent overactivation of the renal sympathetic nervous system drives kidney inflammation and fibrosis. Macrophages contribute to fibrogenesis by secreting various pro-fibrogenic mediators. However, whether the sympathetic nervous system regulates renal fibrosis by modulating macrophage-fibroblast interaction remains unclear. Here, it is demonstrated that norepinephrine (NE)-treated macrophages promoted renal fibroblast activation through the transfer of Notch2 intracellular domain (N2ICD)-enriched extracellular vesicles (EVs) to fibroblasts. Depletion of macrophage mitigated kidney fibrosis in mice subjected to unilateral nephrectomy plus contralateral ischemia-reperfusion injury (Npx-IRI) or repeated low-dose cisplatin (RLDC) regimen. Macrophage-specific deletion of Notch2 or α2B-adrenoceptor disrupted N2ICD-EV formation and protected mice from kidney fibrosis. Mechanistically, N2ICD stabilized Smad3 by preventing its ubiquitin-dependent degradation, thereby enhancing TGF-β signaling to promote fibroblast activation. These findings establish a sympathetic nerve-macrophage-fibroblast axis in renal fibrosis and highlight macrophage-specific Notch2 inhibition as a potential therapeutic strategy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.