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

  • Shuai Yin
  • , Shilin Zhou
  • , Dadui Ren
  • , Jing Zhang
  • , Hong Xin
  • , Xiaozhou He
  • , Hongjian Gao
  • , Jiayun Hou
  • , Feng Zeng
  • , Yunjie Lu
  • , Xuemei Zhang
  • , Min Fan*
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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. 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.

Original languageEnglish
Pages (from-to)651-659
Number of pages9
JournalTissue Engineering - Part A
Volume28
Issue number13-14
DOIs
StatePublished - 1 Jul 2022
Externally publishedYes

Keywords

  • EMT
  • MSC
  • autophagy
  • ceria nanoparticles
  • exosome

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