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Shedding a new light on the circuit HIF‐1 alfa/CA IX/uPAR and other neovascularization related genes by means of post‐transcriptional gene modulators in proliferative retinopathies
Author(s) -
Capaccioli Sergio,
Papucci Laura,
Witort Ewa,
Lapucci Andrea,
Quaglierini Paolo,
Specogna Rebecca,
Lulli Matteo,
Donnini Martino
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.116.5
Subject(s) - urokinase receptor , retinal , neovascularization , cancer research , gene expression , receptor , biology , angiogenesis , gene , microbiology and biotechnology , genetics , biochemistry
Hypoxia‐induced retinal neovascularization underlies three retinal pathogeneses (diabetic retinopathy, AMD and neovascular glaucoma) as the main causes of blindness. Although different growth factors are involved in this process, efficient inhibition of urokinase receptor (uPAR) by specific antibodies suppressing neovascularization suggests, that interaction between uPAR and its ligand uPA plays a major role. In turn, uPAR is transactivated by HIF‐1 alfa, while expression both uPAR and HIF is also controlled at post‐transcriptional level by interactions between AU‐rich cis‐acting elements (ARE) and relevant AU‐Binding Proteins (AUBPs). Despite HIF/uPAR interactions at post‐transcriptional level could serve as optimal therapeutic targets in the management of proliferative retinopathies, this topic has been scarcely investigated so far. Therefore, we aimed to shed a new light on the mechanism underlying these interactions. Preliminary results obtained by modulating HIF, uPAR and other hypoxia‐induced gene expression through peculiar antisense strategies indicated their co‐regulation at post‐transcriptional level as an optimal therapeutic target in proliferative retinopathies