MSCs protect endothelial cells from inflammatory injury partially by secreting STC1

Int Immunopharmacol. 2018 Aug:61:109-118. doi: 10.1016/j.intimp.2018.05.016. Epub 2018 May 29.

Abstract

Inflammatory factors play an important role in the pathogenesis of diabetic vascular complications. Considerable interest in the therapeutic potential of mesenchymal stem cells (MSCs) has recently arisen. The purposes of this study were to investigate the effects of MSCs on endothelial cells under inflammatory conditions and to determine the relevant mechanism underlying these effects. In vitro, after TNF-α stimulation, MSCs-CM treatment significantly restored cell viability, reduced THP-1 cell adhesion and enhanced tube formation capacity via inhibiting ROS overproduction and NF-κB activation, subsequently down-regulating adhesion molecules and chemokines. These effects may be partially due to the up-regulation of uncoupling protein 2 (UCP2) in HUVECs that was induced by the secretion of stanniocalcin 1 (STC1) from MSCs. In vivo, MSCs transplantation ameliorated the progression of diabetes-associated vascular dysfunction by reducing ROS production and down-regulating the expression of adhesion molecules. These results suggest that MSCs protect HUVECs from inflammatory injury partially by secreting STC1. MSCs may be a potential therapeutic approach for the treatment of diabetic vascular complications.

Keywords: Diabetic vascular complication; HUVECs; Inflammation; Mesenchymal stem cells; Stanniocalcin 1; TNF-α.

MeSH terms

  • Cell Adhesion
  • Culture Media, Conditioned / pharmacology*
  • Diabetes Complications / immunology*
  • Glycoproteins / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation / immunology*
  • Mesenchymal Stem Cells / physiology*
  • Morphogenesis
  • Protective Agents / pharmacology*
  • THP-1 Cells
  • Tumor Necrosis Factor-alpha / immunology
  • Uncoupling Protein 2 / metabolism
  • Up-Regulation
  • Vascular Diseases / immunology*

Substances

  • Culture Media, Conditioned
  • Glycoproteins
  • Protective Agents
  • Tumor Necrosis Factor-alpha
  • Uncoupling Protein 2
  • teleocalcin