RGD hydrogel-loaded ADSC extracellular vesicles mitigate uranium-induced renal injury via TLR4/NF-κB pathway inhibition

J Nanobiotechnology. 2025 Feb 17;23(1):114. doi: 10.1186/s12951-025-03176-6.

Abstract

Background: Uranium-induced kidney damage represents a major health concern due to its toxic effects, including mitochondrial dysfunction and inflammation. Mitochondrial DNA (mtDNA)-mediated pyroptosis is a critical pathway in the pathogenesis of renal injury. The toll-like receptor 4 / nuclear factor-kappa B (TLR4/NF-κB) signaling pathway plays a pivotal role in this process. Recent studies have shown that extracellular vesicles derived from adipose-derived stem cells (ADSCs-EVs) possess therapeutic potential due to their anti-inflammatory and regenerative properties. Incorporating ADSCs-EVs into arginine-glycine-aspartate (RGD), hydrogels may enhance their stability and therapeutic efficacy in vivo. This study aims explore the molecular mechanism by which RGD hydrogel-loaded ADSCs-EVs modulate mtDNA-mediated pyroptosis by suppressing the TLR4/NF-κB signaling pathway to alleviate uranium-induced kidney injury.

Results: Repairing mitochondrial dysfunction was found to mitigate mtDNA leakage, thereby inhibiting renal pyroptosis. ADSCs-EVs alleviated uranium-induced renal cell damage by suppressing the TLR4/NF-κB signaling pathway. In vivo animal experiments confirmed that RGD hydrogel-loaded ADSCs-EVs enhanced their stability in the body and improved their therapeutic efficacy against kidney injury.

Conclusion: Our findings reveal that RGD hydrogel-loaded ADSCs-EVs effectively inhibit the TLR4/NF-κB signaling pathway, preventing mtDNA-mediated pyroptosis and alleviating uranium-induced kidney damage. This elucidation provides a novel strategy for utilizing RGD hydrogel-loaded ADSCs-EVs in treating kidney injury.

Keywords: ADSCs-EVs extracellular vesicles; Kidney injury; Mitochondrial DNA; Pyroptosis; RGD hydrogel; TLR4/NF-κB signaling pathway.

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • DNA, Mitochondrial / metabolism
  • Extracellular Vesicles* / metabolism
  • Humans
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacology
  • Kidney / drug effects
  • Kidney / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • NF-kappa B* / metabolism
  • Oligopeptides* / chemistry
  • Oligopeptides* / pharmacology
  • Pyroptosis / drug effects
  • Signal Transduction* / drug effects
  • Toll-Like Receptor 4* / metabolism
  • Uranium*

Substances

  • Toll-Like Receptor 4
  • NF-kappa B
  • Hydrogels
  • Oligopeptides
  • arginyl-glycyl-aspartic acid
  • Uranium
  • DNA, Mitochondrial