Arbutin protects HK-2 cells against high glucose-induced apoptosis and autophagy by up-regulating microRNA-27a

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2940-2947. doi: 10.1080/21691401.2019.1640231.

Abstract

Arbutin (ARB) has been widely used in skin pigmentation disorders. Nevertheless, the involvements of ARB in diabetic nephropathy (DN) are still unknown. We investigated the functions of ARB in high glucose (HG)-induced cell apoptosis and autophagy in HK-2 cells. Cell viability was examined through CCK-8 in HK-2 cells after disposal with 45 mM glucose and ARB (10-50 μM). Flow cytometry and western blot tested cell apoptosis and the related protein levels in HK-2 cells after 45 mM glucose and 50 μM ARB administration. RT-qPCR delved microRNA (miR)-27a expression in HG and ARB co-treated HK-2 cells. Effect of miR-27a on ARB affected cell apoptosis and autophagy was investigated after miR-27a inhibitor transfection. JNK and mTOR pathways were finally assessed by western blot. ARB alleviated HG-induced cell apoptosis, autophagy and regulated the related protein levels in HK-2 cells. MiR-27a expression was reduced in HG-treated cells, but was accelerated in HG and ARB co-treated HK-2 cells with the increased concentration. Inhibition of miR-27a apparently abolished the outcomes of ARB in HG-induced HK-2 cells apoptosis and autophagy. Besides, ARB blocked JNK and mTOR pathways by regulating miR-27a. The findings demonstrated that ARB alleviated apoptosis and autophagy in HG-treated HK-2 cells by regulating miR-27a/JNK/mTOR axis.

Keywords: Diabetic nephropathy; JNK; arbutin; mTOR; microRNA-27a.

MeSH terms

  • Apoptosis / drug effects*
  • Arbutin / pharmacology*
  • Autophagy / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Cytoprotection / drug effects*
  • Dose-Response Relationship, Drug
  • Glucose / adverse effects*
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MicroRNAs / genetics*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism
  • Up-Regulation / drug effects*

Substances

  • MIRN27 microRNA, human
  • MicroRNAs
  • Arbutin
  • TOR Serine-Threonine Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Glucose