As mentioned, it is uncertain whether the pathways for tissue-protection are activated by EPOR homodimers or heterodimers, both, or another receptor conformation (18).
Indeed, inhibition of protein kinase C activity interferes with phosphorylation of the EPOR which suggests that protein kinase C may be an upstream modulator of the EPOR (27).
It appears that angiogenesis is impaired and blood vessels are less responsive to VEGF in the absence of EPOR.
Human neurons, astrocytes and microglial cells produce EPO and express EPOR (54).
Half life is too short for erythropoiesis as continuous EPOR stimulation is required.
EPO-binding to EPORs on erythroid progenitor cells leads to activation of the JAK2-STAT5 signalling pathway and phosphorylation of PI3K and Akt (24) (Figure 1).
EPO and EPOR are expressed in the cerebral cortex, cerebellum, hippocampus, pituitary gland, and spinal cord (Jelkmann, 2005).
Furthermore, abundant expression of EPOR protein has also been found in macrophages, cells that play a pivotal role during wound healing (Haroon et al.
They detected EPO throughout the entire process, and their observed results of EPOR, STAT5 and BAX expressions during retinal and lens differentiation suggest that EPOR may play an important part in the normal development of the eye via apoptosis (Wu et al.
However, they also observed that EPOR expression was similar in both groups.
They speculated that EPO interacts with EPOR in the photoreceptor inner segment, protecting retinal photoreceptors from light-induced apoptotic pathways.
However, they found that intraretinal injections of soluble EPOR reduced neovascularization in 19-day-old mice in a dose dependent manner (25 ng resulted in 65% reduction, 62.