Mesenchymal Stem Cell-Derived Exosomes Attenuate Epithelial-Mesenchymal Transition of HK-2 Cells.

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  • Additional Information
    • Source:
      Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 101466659 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1937-335X (Electronic) Linking ISSN: 19373341 NLM ISO Abbreviation: Tissue Eng Part A Subsets: MEDLINE
    • Publication Information:
      Original Publication: New Rochelle, NY : Mary Ann Liebert, Inc.
    • Subject Terms:
      Exosomes*/metabolism ; Mesenchymal Stem Cells* ; Renal Insufficiency, Chronic*; Epithelial-Mesenchymal Transition ; Fibrosis ; Humans ; Transforming Growth Factor beta1/pharmacology
    • Abstract:
      Renal fibrosis (RF) predisposes patients to an increased risk of progressive chronic kidney disease, and effective treatments remain elusive. Mesenchymal stem cell (MSC)-derived exosomes are considered a new treatment for tissue damage. Our study aimed to investigate the in vitro effects of bone marrow MSC-derived exosomes (BM-MSC-Exs) on transforming growth factor-β1 (TGF-β1)-induced fibrosis in renal tubular epithelial cells (HK-2 cells) and the associated mechanisms. Herein, we found BM-MSC-Exs could inhibit TGF-β1-induced epithelial-mesenchymal transition (EMT) in HK-2 cells, and may involve autophagy activation of BM-MSC-Exs. Moreover, we first reported that after ceria nanoparticles (CeNPs) treatment, the improvements induced by BM-MSC-Ex on EMT were significantly enhanced by upregulating the expression of Nedd4Lof MSCs and promoting the secretion of exosomes, which contained Nedd4L. In addition, Nedd4L could activate autophagy in HK-2 cells. In conclusion, BM-MSC-Ex prevents the TGF-β1-induced EMT of renal tubular epithelial cells by transporting Nedd4L, which activates autophagy. The results of this in vitro experiment may extend to RF, whereby BM-MSC-Ex may also be used as a novel treatment for improving RF. Impact statement Renal fibrosis (RF) is an important pathological change in chronic kidney disease that ultimately leads to end-stage renal failure, and effective treatments remain elusive. In this study, there are two contributions. First, our results suggest that bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-Exs) can prevent transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells through Nedd4L trafficking, which activates autophagy. Second, the improvement effects of BM-MSC-Ex on TGF-β1-induced HK-2 EMT can be enhanced by ceria nanoparticles (CeNPs). The findings in this study may be extended to RF: BM-MSC-Exs may be used as a novel treatment to improve RF.
    • Contributed Indexing:
      Keywords: EMT; MSC; autophagy; ceria nanoparticles; exosome
    • Accession Number:
      0 (Transforming Growth Factor beta1)
    • Publication Date:
      Date Created: 20220112 Date Completed: 20220718 Latest Revision: 20220819
    • Publication Date:
      20240104
    • Accession Number:
      10.1089/ten.TEA.2021.0190
    • Accession Number:
      35019728