Loss of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) in the Diabetic Retina: Role of Matrix Metalloproteinases

Investigative Ophthalmology & Visual Science
Randa S Eshaq, Norman R Harris

Abstract

To test the hypothesis that high glucose and matrix metalloproteinases (MMPs) contribute to the diabetes-induced loss of platelet endothelial cell adhesion molecule-1 (PECAM-1) in the retinal microvasculature. PECAM-1 and MMP protein, activity, and interactions with PECAM-1 were assessed using western blotting, zymography, immunofluorescence, or coimmunoprecipitation assays. These assays were conducted using primary rat retinal microvascular endothelial cells (RRMECs) grown either in normal glucose (5 mM) or high glucose (25 mM) conditions and using retinas collected from streptozotocin-induced diabetic or control rats. The broad-spectrum MMP inhibitor GM6001 was administered in vivo and in vitro to ascertain the role of MMPs in the hyperglycemia-induced loss of PECAM-1. A dramatic decrease in PECAM-1 (western blotting, immunofluorescence) was observed in both the diabetic retina and in hyperglycemic RRMECs. The decrease in PECAM-1 was accompanied by a significant increase in the presence and activity of matrix metalloproteinase-2 (MMP-2) (but not matrix metalloproteinase-9 [MMP-9]) in the diabetic plasma (P < 0.05) and in hyperglycemic RRMECs (P < 0.05). Moreover, RRMEC PECAM-1 significantly decreased when treated with plasma ...Continue Reading

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Citations

Oct 20, 2019·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Randa S Eshaq, Norman R Harris
Sep 24, 2020·Journal of Diabetes Research·Anna S Huerta-DelgadoLeticia Elizondo-Montemayor
Apr 9, 2019·Biorheology·Norman R HarrisPatsy R Carter
Feb 16, 2021·Proteomics. Clinical Applications·Natasha LetunicaChantal Attard
Jun 9, 2021·The British Journal of Ophthalmology·Joseph R AbrahamJustis P Ehlers

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Datasets Mentioned

BETA
GM6001

Methods Mentioned

BETA
immunoprecipitation assay
protein assay
coimmunoprecipitation
immunoprecipitation

Software Mentioned

Prism
ImageJ
PROSPER
GraphPad

Related Concepts

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