(Pro)renin receptor is expressed in human retinal pigment epithelium and participates in extracellular matrix remodeling

Oscar Alcazar, Scott W. Cousins, Gary E. Striker, Maria E. Marin-Castano

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The (pro)renin receptor (PRR) is believed to potentiate the renin-angiotensin system (RAS), conferring to prorenin, a likely pathological role at tissue level. The PRR has been identified in the microvascular endothelial cells of the retina, in which it seems to be involved in pathological neovascularization processes. In the present study, we sought to explore PRR expression and prorenin action in human retinal pigment epithelium (RPE) cells, as well as its potential implication in extracellular matrix (ECM) turnover. Isolated RPE cells from donor human eyes as well as freshly isolated human retinas demonstrated expression of PRR at mRNA and protein levels. Moreover, we demonstrate that PRR expressed in the RPE cells is functional, as shown by prorenin-induced increases in Erk1/2 phosphorylation. PRR expression was also shown to be regulated by its main physiological agonist prorenin. We found evidence that the PRR may be involved in ECM-remodeling processes through a prorenin-induced upregulation of type I collagen. Immunostaining analysis of human retinas revealed higher PRR and type I collagen expression in the RPE of eye donors with dry age-related macular degeneration (AMD) and hypertension, supporting the in vitro findings using human-isolated RPE cells. Taken together, the present study demonstrates for the first time that the PRR is expressed in human RPE and suggests a molecular mechanism by which hypertension may exacerbate the pathology of dry AMD.

Original languageEnglish (US)
Pages (from-to)638-647
Number of pages10
JournalExperimental Eye Research
Volume89
Issue number5
DOIs
StatePublished - Nov 1 2009

Keywords

  • (pro)renin receptor
  • age-related macular degeneration
  • hypertension
  • prorenin
  • retinal pigment epithelium

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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