Molecular responses of choroidal endothelial cells to elastin derived peptides through the elastin-binding protein (GLB1)

Jessica M Skeie; Jasmine Hernandez; Aleksander Hinek; Robert F Mullins

doi:10.1016/j.matbio.2011.11.003

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Molecular responses of choroidal endothelial cells to elastin derived peptides through the elastin-binding protein (GLB1)

Journal article

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Molecular responses of choroidal endothelial cells to elastin derived peptides through the elastin-binding protein (GLB1)

Jessica M Skeie, Jasmine Hernandez, Aleksander Hinek and Robert F Mullins

Matrix Biology, Vol.31(2), pp.113-119

03/2012

DOI: 10.1016/j.matbio.2011.11.003

PMCID: PMC3288713

PMID: 22178079

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https://www.ncbi.nlm.nih.gov/pmc/articles/3288713View

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Abstract

Neovascular AMD involves the activation of choroidal endothelial cells to increase their inflammatory and angiogenic behaviors. Elastin derived peptides (EDPs) can elicit some of these phenotypic changes in endothelial cells. This investigation was performed to follow up on those findings by determining a receptor for these peptides in the human eye as well as evaluating the effects of elevated EDPs on choroidal cells in vitro and in vivo. The expression of elastin receptor genes including GLB1 was analyzed using reverse transcription PCR. Migration of choroidal endothelial cells was quantified in the presence of inhibitors to different EDP binding proteins. C57BL6 mice were injected with EDPs and studied by electroretinography, transmission electron microscopy, and microarray analysis. An alternatively spliced form of beta-galactosidase (GLB1) is present on human choroidal endothelial cells and acts as a receptor for EDPs. Elevated levels of circulating EDPs do not affect retinal function in the mouse, but do increase the expression and deposition of collagen IV in the RPE/choroid complex. EDPs may play a role in neovascular AMD by binding to and inducing neovascular phenotypes in choroidal endothelial cells through their receptor, GLB1. These peptides also cause an increased mRNA expression and deposition of collagen IV in the RPE/choroid, which may alter diffusion properties between the retina and choriocapillaris. ► Abnormal choroidal angiogenesis can occur in age-related macular degeneration. ► Elastin fragments from Bruch's membrane may induce angiogenesis. ► The mechanism of choroidal endothelial cell activation by elastin was explored. ► We found expression of elastin receptor on human choroidal EC. ► Circulating elastin pepides alter ocular gene expression of ECM genes.

Macular degeneration

Macula

Choroid

Bruch's membrane

Elastin

Details

Title: Subtitle: Molecular responses of choroidal endothelial cells to elastin derived peptides through the elastin-binding protein (GLB1)
Creators: Jessica M Skeie - Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA, USA
Jasmine Hernandez - Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA, USA
Aleksander Hinek - Division of Cardiovascular Research, The Hospital for Sick Children, Toronto, ON, Canada
Robert F Mullins - Department of Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Matrix Biology, Vol.31(2), pp.113-119
DOI: 10.1016/j.matbio.2011.11.003
PMID: 22178079
PMCID: PMC3288713
NLM abbreviation: Matrix Biol
ISSN: 0945-053X
eISSN: 1569-1802
Publisher: Elsevier B.V
Grant note: DOI: 10.13039/100000053, name: National Eye Institute, award: EY017451
Language: English
Date published: 03/2012
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983980290902771

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