Prolyl Hydroxylase Inhibitor-Mediated HIF Activation Drives Transcriptional Reprogramming in Retinal Pigment Epithelium: Relevance to Chronic Kidney Disease.

ABSTRACT: Chronic kidney disease (CKD)-associated anemia is a global health concern and is linked to vascular and ocular complications. Hypoxia-inducible factor (HIF) stabilizers, or HIF prolyl hydroxylase inhibitors (PHIs), are promising candidates for the treatment of CKD-associated anemia. Since hypoxia and angiogenesis are involved in eye diseases, this study examined the effects of HIF-PHIs on metabolism and gene expression in retinal pigment epithelium (RPE) cells. Results revealed that PHIs differentially induced angiogenic (VEGFA, ANG) and glycolytic (PDK1, GLUT1) gene expression, with Roxadustat causing the strongest transcriptional changes. However, Roxadustat-induced angiogenic signals did not promote endothelial tube formation. Moreover, it did not induce oxidative stress, inflammation,

SUBMITTER: Gall T 

PROVIDER: S-EPMC12293706 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature