Targeting CH25H/25HC-ferroptosis axis: a novel mechanism of MSC-EVs mediated renoprotection in ischemic AKI

Quick Facts

  • Publication title: Targeting CH25H/25HC-ferroptosis axis: a novel mechanism of MSC-EVs mediated renoprotection in ischemic AKI
  • Journal: J Nanobiotechnology
  • Year: 2026
  • DOI: 10.1186/s12951-026-04339-9
  • PMID/PMCID: 41957810; PMC13390321

Research overview

Acute kidney injury (AKI) remains a major clinical challenge due to the lack of effective interventions. While mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show therapeutic promise for AKI, their exact mechanisms are largely to be understood.

Key findings

MSC-EVs preferentially targeted injured kidneys and significantly improved renal function, ameliorated tubular injury, and suppressed inflammation in IRI-AKI.

RNA sequencing and targeted metabolomics revealed substantial dysregulation of steroid metabolism after IRI, marked by activation of the cholesterol 25-hydroxylase (CH25H)/25-hydroxycholesterol (25HC) axis.

Importantly, accumulated 25HC induced lipid peroxidation and ferroptosis in tubular epithelial cells.

MSC-EVs treatment reversed these pathological changes by downregulating CH25H, lowering 25HC levels, and restoring redox homeostasis.

Study design

Human umbilical cord-derived MSC-EVs were isolated, characterized, and tested in a murine bilateral renal ischemia reperfusion injury (bIRI) model and in hypoxia/reoxygenation (H/R) treated tubular epithelial cells in vitro.

Integrated transcriptomic, miRNA, and biochemical analyses were performed to elucidate the metabolic pathways and molecular mechanisms underlying the renoprotective effects of MSC-EVs.

Echo Biotech Role

Echo Biotech contributed EV isolation and purification, miRNA profiling/sequencing and bioinformatic analysis; the study also used or cited Exosupur®.

Related platforms: Exoomics®, Research Reagents & Tools

Related services and capabilities: Cell-Culture Supernatant EV Isolation & Purification, EV miRNA Profiling / Sequencing, Research Reagent / Product Supply

Related products or reagents: Exosupur® EV Isolation/Purification Kit

References

Original publication: Targeting CH25H/25HC-ferroptosis axis: a novel mechanism of MSC-EVs mediated renoprotection in ischemic AKI Journal of nanobiotechnology. 2026. DOI: 10.1186/s12951-026-04339-9. PMID/PMCID: 41957810; PMC13390321.