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

Abstract

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. Graphical abstract

Keywords

• RGD hydrogel
• ADSCs-EVs extracellular vesicles
• TLR4/NF-κB signaling pathway
• Mitochondrial DNA
• Pyroptosis
• Kidney injury