Hepatocyte growth factor prevents pericyte loss in diabetic retinopathy

Microvasc Res. 2021 Jan:133:104103. doi: 10.1016/j.mvr.2020.104103. Epub 2020 Nov 9.

Abstract

Diabetic retinopathy (DR) is a disease that causes blindness due to vascular leakage or abnormal angiogenesis. Hepatocyte growth factor (HGF) is increased in the serum or vitreous fluid in proliferative diabetic retinopathy (PDR) patients, although the effect of HGF on the blood vessels remains unclear. This study focused on the effect of HGF on pericyte (PC) survival and endothelial cell (EC) permeability. It was demonstrated that HGF was increased in the diabetic mouse retina. However, HGF prevented PC apoptosis caused by TNF-α, which increased in the diabetic retinas both in vitro and in vivo. In addition, HGF was involved in PC survival by increasing the Akt signaling pathway. Moreover, HGF strengthened the EC tight junction in co-cultures of PCs and ECs by promoting PC survival, thereby reducing EC permeability. These results suggest that HGF may play a role in the prevention of increased vascular leakage by inhibiting the PC loss that occurs in DR to some extent. However, careful HGF reduction in DR might avoid an increase in PC loss.

Keywords: Diabetic retinopathy; Endothelial cell permeability; Hepatocyte growth factor; Pericyte apoptosis; Pericyte loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Coculture Techniques
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / metabolism
  • Diabetic Retinopathy / pathology
  • Disease Models, Animal
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Hepatocyte Growth Factor / metabolism
  • Hepatocyte Growth Factor / pharmacology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pericytes / drug effects*
  • Pericytes / metabolism
  • Pericytes / pathology
  • Permeability
  • Phosphatidylinositol 3-Kinase / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Retinal Vessels / drug effects*
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism
  • Tight Junctions / pathology

Substances

  • HGF protein, human
  • HGF protein, mouse
  • Hepatocyte Growth Factor
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases