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miR-21-5p in extracellular vesicles obtained from adipose tissue-derived stromal cells facilitates tubular epithelial cell repair in acute kidney injury

  • Zhixiang Bian
    Affiliations
    Department of Nephrology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China
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  • Xiangxiang Wang
    Affiliations
    Department of Nephrology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China
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  • Rui Zhu
    Correspondence
    Correspondence: Shunjie Chen and Rui Zhu, Department of Nephrology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, No. 1279 Sanmen Rd, 19th Floor, Shanghai 200434, People's Republic of China
    Affiliations
    Department of Nephrology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China
    Search for articles by this author
  • Shunjie Chen
    Correspondence
    Correspondence: Shunjie Chen and Rui Zhu, Department of Nephrology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, No. 1279 Sanmen Rd, 19th Floor, Shanghai 200434, People's Republic of China
    Affiliations
    Department of Nephrology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China
    Search for articles by this author
Published:October 14, 2022DOI:https://doi.org/10.1016/j.jcyt.2022.08.002

      Abstract

      Background aims

      Acute kidney injury (AKI) is often associated with poor patient outcomes. Extracellular vesicles (EVs) have a marked therapeutic effect on renal recovery. This study sought to explore the functional mechanism of EVs from adipose tissue-derived stromal cells (ADSCs) in tubular epithelial cell (TEC) repair in AKI.

      Methods

      ADSCs were cultured and EVs were isolated and identified. In vivo and in vitro AKI models were established using lipopolysaccharide (LPS).

      Results

      EVs increased human kidney 2 (HK-2) cell viability; decreased terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and levels of kidney injury molecule 1, cleaved caspase-1, apoptosis-associated speck-like protein containing a CARD, gasdermin D-N, IL-18 and IL-1β; and elevated pro-caspase-1. EVs carried miR-21-5p into LPS-induced HK-2 cells. Silencing miR-21-5p partly eliminated the ability of EVs to suppress HK-2 cell pyroptosis and inflammation. miR-21-5p targeted toll-like receptor 4 (TLR4) and inhibited TEC pyroptosis and inflammation after AKI by inhibiting TLR4. TLR4 overexpression blocked the inhibitory effects of EVs on TEC pyroptosis and inflammation. EVs suppressed the nuclear factor-κB/NOD-like receptor family pyrin domain-containing 3 (NF-κB/NLRP3) pathway via miR-21-5p/TLR4. Finally, AKI mouse models were established and in vivo assays verified that ADSC-EVs reduced TEC pyroptosis and inflammatory response and potentiated cell repair by mediating miR-21-5p in AKI mice.

      Conclusions

      ADSC-EVs inhibited inflammation and TEC pyroptosis and promoted TEC repair in AKI by mediating miR-21-5p to target TLR4 and inhibiting the NF-κB/NLRP3 pathway.

      Graphical Abstract

      Key Words

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