Exosomes from miR-20b-3p-overexpressing stromal cells ameliorate calcium oxalate deposition in rat kidney

J Cell Mol Med. 2019 Nov;23(11):7268-7278. doi: 10.1111/jcmm.14555. Epub 2019 Sep 5.

Abstract

Hyperoxaluria-induced calcium oxalate (CaOx) deposition is the key factor in kidney stone formation, for which adipose-derived stromal cells (ADSCs) have been used as a therapeutic treatment. Studies revealed that miR-20b-3p is down-regulated in hypercalciuric stone-forming rat kidney. To investigate whether ADSC-derived miR-20b-3p-enriched exosomes protect against kidney stones, an ethylene glycol (EG)-induced hyperoxaluria rat model and an in vitro model of oxalate-induced NRK-52E cells were established to explore the protective mechanism of miR-20b-3p. The results showed that miR-20b-3p levels were decreased following hyperoxaluria in the urine of patients and in kidney tissues from animal models. Furthermore, treatment with miR-20b-3p-enriched exosomes from ADSCs protected EG-induced hyperoxaluria rats, and cell experiments confirmed that co-culture with miR-20b-3p-enriched exosomes alleviated oxalate-induced cell autophagy and the inflammatory response by inhibiting ATG7 and TLR4. In conclusion, ADSC-derived miR-20b-3p-enriched exosomes protected against kidney stones by suppressing autophagy and inflammatory responses.

Keywords: calcium oxalate deposition; exosomes; miR-20b-3p; microRNAs; stromal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Apoptosis
  • Autophagy
  • Calcium Oxalate / toxicity*
  • Cell Adhesion
  • Cell Proliferation
  • Cells, Cultured
  • Exosomes / genetics*
  • Humans
  • Hyperoxaluria / chemically induced
  • Hyperoxaluria / genetics
  • Hyperoxaluria / pathology
  • Hyperoxaluria / prevention & control*
  • Male
  • MicroRNAs / administration & dosage*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stromal Cells / drug effects*
  • Stromal Cells / metabolism
  • Stromal Cells / pathology

Substances

  • MIRN20 microRNA, rat
  • MicroRNAs
  • Calcium Oxalate