RGD Reference Report - Erythropoietin is a hypoxia inducible factor-induced protective molecule in experimental autoimmune neuritis. - Rat Genome Database

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Erythropoietin is a hypoxia inducible factor-induced protective molecule in experimental autoimmune neuritis.

Authors: Luo, B  Jiang, M  Yang, X  Zhang, Z  Xiong, J  Schluesener, HJ  Zhang, Z  Wu, Y 
Citation: Luo B, etal., Biochim Biophys Acta. 2013 Aug;1832(8):1260-70. doi: 10.1016/j.bbadis.2013.04.015. Epub 2013 Apr 17.
RGD ID: 10395381
Pubmed: PMID:23603807   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbadis.2013.04.015   (Journal Full-text)

Experimental autoimmune neuritis (EAN), an autoantigen-specific T-cell-mediated disease model for human demyelinating inflammatory disease of the peripheral nervous system, is characterized by self-limitation. Here we investigated the regulation and contribution of erythropoietin (EPO) in EAN self-limitation. In EAN sciatic nerves, hypoxia, and protein and mRNA levels of hypoxia-inducible factor 1alpha (HIF-1alpha), HIF-2alpha, EPO and EPO receptor (EPOR) were induced in parallel at disease peak phase but reduced at recovery periods. Further, the deactivation of HIF reduced EAN-induced EPO/EPOR upregulation in EAN, suggesting the central contribution of HIF to EPO/EPOR induction. The deactivation of EPOR signalling exacerbated EAN progression, implying that endogenous EPO contributed to EAN recovery. Exogenous EPO treatment greatly improved EAN recovery. In addition, EPO was shown to promote Schwann cell survival and myelin production. In EAN, EPO treatment inhibited lymphocyte proliferation and altered helper T cell differentiation by inducing increase of Foxp3(+)/CD4(+) regulatory T cells and decrease of IFN-gamma(+)/CD4(+) Th1 cells. Furthermore, EPO inhibited inflammatory macrophage activation and promoted its phagocytic activity. In summary, our data demonstrated that EPO was induced in EAN by HIF and contributed to EAN recovery, and endogenous and exogenous EPO could effectively suppress EAN by attenuating inflammation and exerting direct cell protection, indicating that EPO contributes to the self-recovery of EAN and could be a potent candidate for treatment of autoimmune neuropathies.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Epas1  (endothelial PAS domain protein 1)
Hif1a  (hypoxia inducible factor 1 subunit alpha)

Genes (Mus musculus)
Epas1  (endothelial PAS domain protein 1)
Hif1a  (hypoxia inducible factor 1, alpha subunit)

Genes (Homo sapiens)
EPAS1  (endothelial PAS domain protein 1)
HIF1A  (hypoxia inducible factor 1 subunit alpha)


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