Mesenchymal Stem Cells Ameliorated Glucolipotoxicity in HUVECs through TSG-6

Int J Mol Sci. 2016 Apr 1;17(4):483. doi: 10.3390/ijms17040483.


Glucolipotoxicity is one of the critical causal factors of diabetic complications. Whether mesenchymal stem cells (MSCs) have effects on glucolipotoxicity in human umbilical vein endothelial cells (HUVECs) and mechanisms involved are unclear. Thirty mM glucose plus 100 μM palmitic acid was used to induce glucolipotoxicity in HUVECs. MSCs and HUVECs were co-cultured at the ratio of 1:5 via Transwell system. The mRNA expressions of inflammatory factors were detected by RT-qPCR. The productions of reactive oxygen species (ROS), cell cycle and apoptosis were analyzed by flow cytometry. The tumor necrosis factor-α stimulated protein 6 (TSG-6) was knockdown in MSCs by RNA interference. High glucose and palmitic acid remarkably impaired cell viability and tube formation capacity, as well as increased the mRNA expression of inflammatory factors, ROS levels, and cell apoptosis in HUVECs. MSC co-cultivation ameliorated these detrimental effects in HUVECs, but no effect on ROS production. Moreover, TSG-6 was dramatically up-regulated by high glucose and fatty acid stimulation in both MSCs and HUVECs. TSG-6 knockdown partially abolished the protection mediated by MSCs. MSCs had protective effects on high glucose and palmitic acid induced glucolipotoxicity in HUVECs, and TSG-6 secreted by MSCs was likely to play an important role in this process.

Keywords: HUVECs; MSCs; glucolipotoxicity; inflammation; tumor necrosis factor-α stimulated protein 6 (TSG-6).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Adhesion Molecules / antagonists & inhibitors
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chemokines / genetics
  • Chemokines / metabolism
  • Coculture Techniques
  • Cytokines / genetics
  • Cytokines / metabolism
  • Flow Cytometry
  • Glucose / toxicity*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Microscopy, Fluorescence
  • NF-kappa B / metabolism
  • Palmitic Acid / toxicity*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Reactive Oxygen Species / metabolism
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation / drug effects


  • Cell Adhesion Molecules
  • Chemokines
  • Cytokines
  • NF-kappa B
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • TNFAIP6 protein, human
  • Palmitic Acid
  • Glucose