2. Academic Validation
  3. RGD hydrogel-loaded ADSC extracellular vesicles mitigate uranium-induced renal injury via TLR4/NF-κB pathway inhibition

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.
Xi Chen # 1 2,  Chun-Mei Dai # 2 3,  Bin Zhang 2 3,  Wan-Xin Zhang 2 3,  Zheng-Hong Huang 2 4,  Jiu-Yi Jiang 2 3,  Shi-Qi Hu 1,  Jia-Hua Ma 5,  Jia-Fu Feng 6 7
Affiliations

Affiliations

  • 1 School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, 621010, China.
  • 2 NHC Key Laboratory of Nuclear Technology Medical Transformation (MIANYANG CENTRAL HOSPITAL), Affiliated School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, Sichuan, 621000, China.
  • 3 Department of Medical Laboratory, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China.
  • 4 College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.
  • 5 School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, 621010, China. jiahuama@swust.edu.cn.
  • 6 School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan, 621010, China. jiafufeng@sc-mch.cn.
  • 7 NHC Key Laboratory of Nuclear Technology Medical Transformation (MIANYANG CENTRAL HOSPITAL), Affiliated School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, Sichuan, 621000, China. jiafufeng@sc-mch.cn.
  • # Contributed equally.
PMID: 39962465 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.

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