Linoleic Acid Enhances Renal Tubular Epithelial Cells Autophagy Caused by Calcium Oxalate Monohydrate Crystals

J Cell Mol Med. 2024 Dec;28(24):e70250. doi: 10.1111/jcmm.70250.

Abstract

High intake of dietary linoleic acid may increase the incidence of many diseases. The aim of this research is to examine the impact of linoleic acid on the damage caused by calcium oxalate kidney stones on renal tubular epithelial cells. Calcium oxalate monohydrate (COM) crystals were prepared and used to treat HK-2 cells, which were further treated with different concentrations of linoleic acid in vitro. Also, a small-interfering RNA lentiviral vector of milk fat globule epidermal growth factor 8 (MFGE8) was constructed and transfected into HK-2 cells. The cell viability, level of intracellular ROS and autophagy were tested. In vivo experiments were also carried out with a rat model for renal urolithiasis treated with linoleic acid. The results indicated that COM crystals promoted crystal deposition and apoptosis, increased levels of intracellular Ca2+ and ROS levels and inhibited the proliferation of HK-2 cells. Linoleic acid exacerbated the damage of COM crystal-treated HK-2 cells and renal tubular epithelial cells of the rat model for renal urolithiasis, which can be partially reversed by downregulation of MFGE8. These results collectively suggest that linoleic acid might enhance the damage of renal tubular epithelial cells caused by COM crystals.

Keywords: MFGE8; ROS; apoptosis; calcium oxalate kidney stones; linoleic acid.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Autophagy* / drug effects
  • Calcium / metabolism
  • Calcium Oxalate* / metabolism
  • Calcium Oxalate* / toxicity
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Crystallization
  • Epithelial Cells* / drug effects
  • Epithelial Cells* / metabolism
  • Epithelial Cells* / pathology
  • Humans
  • Kidney Calculi / etiology
  • Kidney Calculi / metabolism
  • Kidney Calculi / pathology
  • Kidney Tubules* / drug effects
  • Kidney Tubules* / metabolism
  • Kidney Tubules* / pathology
  • Linoleic Acid* / pharmacology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species* / metabolism

Substances

  • Calcium Oxalate
  • Linoleic Acid
  • Reactive Oxygen Species
  • Calcium