Combination with miR-124a improves the protective action of BMSCs in rescuing injured rat podocytes from abnormal apoptosis and autophagy

J Cell Biochem. 2018 Sep;119(9):7166-7176. doi: 10.1002/jcb.26771. Epub 2018 Jun 15.

Abstract

This in vitro study was performed to identify the role of miR-124a in bone marrow stromal stem cells (BMSCs) therapy for H2 O2 -induced rat podocyte injury, and determine whether combination treatment with miR-124a could improve the protective effect of BMSCs. Cell viability of podocytes was detected by CCK-8 assay. Detection of ROS level, apoptotic rate, and autophagy rate was carried out using flow cytometry assays. Oxidative stress parameters were analyzed using the ELISA assays. MiR-124a and mRNA levels were determined using real-time PCR. Protein expression was detected using Western blotting. Our study revealed a pivotal role of miR-124a in the protective action of BMSCs on podocyte injury driven by oxidative stress. BMSCs could rescue injured podocytes from aberrant apoptosis and autophagy by regulating cleaved caspase-3, Bax, Bcl-2, LC3-II/I, and p62. Suppression of the PI3 K/Akt/mTOR signaling pathway is likely one of the main mechanisms underlying the protective action of BMSCs transfected with miR-124a. Our study revealed that miR-124a further improves the protective effect of BMSCs in injured podocytes. Thus, the combination of BMSCs and microRNAs could be a beneficial treatment for renal diseases in the near future.

Keywords: BMSCs; apoptosis; autophagy; miR-124a; podocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Autophagy*
  • Caspase 3 / metabolism
  • Cell Survival / drug effects
  • Cell- and Tissue-Based Therapy / methods
  • Cells, Cultured
  • Class Ia Phosphatidylinositol 3-Kinase
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / therapy
  • Hydrogen Peroxide / pharmacology
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Microtubule-Associated Proteins / metabolism
  • Molecular Mimicry
  • Oxidative Stress
  • Phosphoinositide-3 Kinase Inhibitors
  • Podocytes / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Sequestosome-1 Protein / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Transfection
  • bcl-2-Associated X Protein / metabolism

Substances

  • LC3 protein, rat
  • MIRN124 microRNA, human
  • MicroRNAs
  • Microtubule-Associated Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Sequestosome-1 Protein
  • Sqstm1 protein, rat
  • bcl-2-Associated X Protein
  • Hydrogen Peroxide
  • PIK3R2 protein, rat
  • mTOR protein, rat
  • Class Ia Phosphatidylinositol 3-Kinase
  • TOR Serine-Threonine Kinases
  • Casp3 protein, rat
  • Caspase 3