title: Pathologic Roles of Receptor-Associated Prorenin System in Idiopathic Epiretinal Membrane.
abstract: Receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to (pro)renin receptor [(P)RR] dually activates tissue renin-angiotensin system (RAS) and RAS-independent signaling via (P)RR. The aim of this study is to determine the association of RAPS with idiopathic epiretinal membrane (iERM). Reverse transcription-PCR indicated the expression of RAPS components, including (P)RR and Ang II type 1 receptor (AT1R), in iERM tissues and human Müller glial cell line. Double-labeling analyses demonstrated that (P)RR and AT1R were detected in cells positive for glial fibrillary acidic protein, a marker for glial cells, and co-localized with prorenin and angiotensinogen, respectively. Administration of prorenin to Müller glial cells enhanced mRNA expression of fibroblast growth factor 2, while Ang II application stimulated the expression of glial cell line-derived neurotrophic factor, nerve growth factor, and transforming growth factor-β1. These expression levels induced by prorenin or Ang II were reversed by (P)RR or AT1R blockade, respectively. Immunofluorescence revealed tissue co-localization of (P)RR and AT1R with the products of the upregulated genes in vitro. The present findings suggest the involvement of RAPS in the pathogenesis of iERM.
authors.affiliation: Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638, Japan.|Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638, Japan.|Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kanda
authors.affiliation: Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638, Japan.|Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Noda
authors.affiliation: Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Saito
authors.affiliation: Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638, Japan.|Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000494:pharmacology; D002460:Cell Line; D063928:Ependymoglial Cells / Q000187:drug effects / Q000378:metabolism; D019773:Epiretinal Membrane / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D012083:Renin / Q000235:genetics* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D000093342:Prorenin Receptor
chemical_list: D044140:Receptor, Angiotensin, Type 1; D011956:Receptors, Cell Surface; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D000804:Angiotensin II; D012083:Renin; D000093342:Prorenin Receptor