Suppression of protein kinase C-ζ attenuates vascular leakage via prevention of tight junction protein decrease in diabetic retinopathy.

Abstract

To investigate the effect of protein kinase C (PKC)-ζ inhibition on vascular leakage in diabetic retinopathy, streptozotocin-induced diabetic mice were intravitreously injected with siPKC-ζ. According to the fluorescein angiography of the retinal vessels, suppression of PKC-ζ effectively attenuated vascular leakage in diabetic retina. Further evaluation on the retina with western blot analysis and immunohistochemistry revealed accompanying restoration of tight junction proteins on retinal vessels. As two major contributors to vascular leakage in diabetic retinopathy, vascular endothelial growth factor (VEGF) and advanced glycation end products (AGEs) were investigated on the tight junction protein expression in endothelial cells. Inhibition of PKC-ζ attenuated VEGF-induced decrease of tight junction proteins and accompanying hyperpermeability in human retinal microvascular endothelial cells (HRMECs). PKC-ζ inhibition also attenuated AGE-induced decrease of tight junction proteins in HRMECs. Our findings suggest that inhibition of PKC-ζ could be an alternative treatment option for compromised blood-retinal barrier in diabetic retinopathy.

• Authors: Hyun Beom Song, Hyoung-Oh Jun, Jin Hyoung Kim, Young Suk Yu, Kyu Won Kim, Jeong Hun Kim
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 444 Issue 1 Pg. 63-8 (Jan 31 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24434146 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Glycation End Products, Advanced
• RNA, Small Interfering
• Tight Junction Proteins
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• protein kinase C zeta
• Protein Kinase C

Topics

• Animals
• Blood-Retinal Barrier
• Capillary Permeability
• Diabetes Mellitus, Experimental (genetics, metabolism)
• Diabetic Retinopathy (genetics, metabolism)
• Endothelial Cells (metabolism)
• Glycation End Products, Advanced (metabolism)
• Humans
• Mice
• Mice, Inbred C57BL
• Protein Kinase C (antagonists & inhibitors, genetics, metabolism)
• RNA, Small Interfering (genetics)
• Retinal Vessels (metabolism)
• Tight Junction Proteins (metabolism)
• Tight Junctions (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)