The Expression of Decidual Protein Induced by Progesterone (DEPP) is Controlled by Three Distal Consensus Hypoxia Responsive Element (HRE) in Hypoxic Retinal Epithelial Cells.

Hypoxia affects the development and/or progression of several retinopathies. Decidual protein induced by progesterone () has been identified as a hypoxia-responsive gene that may be part of cellular pathways such as autophagy and connected to retinal diseases. To increase our understanding of regulation in the eye, we defined its expression pattern in mouse and human retina and retinal pigment epithelium (RPE). Interestingly, expression was increased in an age-dependent way in the central human RPE. We showed that was regulated by hypoxia in the mouse retina and eyecup and that this regulation was controlled by hypoxia-inducible transcription factors 1 and 2 (HIF1 and HIF2). Furthermore, we identified three hypoxia response elements (HREs) about 3.5 kb proximal to the transcriptional start site that were responsible for hypoxic induction of in a human RPE cell line. Comparative genomics analysis suggested that one of the three HREs resides in a highly conserved genomic region. Collectively, we defined the molecular elements controlling hypoxic induction of in an RPE cell line, and provided evidence for an enrichment of in the aged RPE of human donors. This makes an interesting gene to study with respect to aging and age-related retinal pathologies.