Role of hypoxia-mediated cellular prion protein functional change in stem cells and potential application in angiogenesis (Review)

Abstract

Cellular prion protein (PrPC) can replace other pivotal molecules due to its interaction with several partners in performing a variety of important biological functions that may differ between embryonic and mature stem cells. Recent studies have revealed major advances in elucidating the putative role of PrPC in the regulation of stem cells and its application in stem cell therapy. What is special about PrPC is that its expression may be regulated by hypoxia-inducible factor (HIF)-1 alpha, which is the transcriptional factor of cellular response to hypoxia. Hypoxic conditions have been known to drive cellular responses that can enhance cell survival, differentiation and angiogenesis through adaptive processes. Our group recently reported hypoxia-enhanced vascular repair of endothelial colony-forming cells on ischemic injury. Hypoxia-induced AKT/signal transducer and activator of transcription 3 phosphorylation eventually increases neovasculogenesis. In stem cell biology, hypoxia promotes the expression of growth factors. According to other studies, aspects of tissue regeneration and cell function are influenced by hypoxia, which serves an essential role in stem cell HIF-1 alpha signaling. All these data suggest the possibility that hypoxia-mediated PrPC serves an important role in angiogenesis. Therefore, the present review summarizes the characteristics of PrPC, which is produced by HIF-1 alpha in hypoxia, as it relates to angiogenesis.