Erythropoietin Receptor/β Common Receptor: A Shining Light on Acute Kidney Injury Induced by Ischemia-Reperfusion

Acute kidney injury (AKI) is a health problem worldwide, but there is a lack of early diagnostic biomarkers and target-specific treatments. Ischemia-reperfusion (IR), a major cause of AKI, not only induces kidney injury, but also stimulates the self-defense system including innate immune responses to limit injury. One of these responses is the production of erythropoietin (EPO) by adjacent normal tissue, which is simultaneously triggered, but behind the action of its receptors, either by the homodimer EPO receptor (EPOR)(2) mainly involved in erythropoiesis or the heterodimer EPOR/beta common receptor (EPOR/beta cR) which has a broad range of biological protections. EPOR/beta cR is expressed in several cell types including tubular epithelial cells at low levels or absent in normal kidneys, but is swiftly upregulated by hypoxia and inflammation and also translocated to cellular membrane post IR. EPOR/beta cR mediates anti-apoptosis, anti-inflammation, pro-regeneration, and remodeling via the P beta K/Akt, STAT3, and MAPK signaling pathways in AKI. However, the precise roles of EPOR/beta cR in the pathogenesis and progression of AKI have not been well defined, and its potential as an earlier biomarker for AKI diagnosis and monitoring repair or chronic progression requires further investigation. Here, we review biological functions and mechanistic signaling pathways of EPOR/beta cR in AKI, and discuss its potential clinical applications as a biomarker for effective diagnosis and predicting prognosis, as well as directing cell target drug delivery.