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The erythropoietin receptor is a downstream effector of Klotho-induced cytoprotection.

Authors: Hu, MC  Shi, M  Cho, HJ  Zhang, J  Pavlenco, A  Liu, S  Sidhu, S  Huang, LJ  Moe, OW 
Citation: Hu MC, etal., Kidney Int. 2013 Sep;84(3):468-81. doi: 10.1038/ki.2013.149. Epub 2013 May 1.
Pubmed: (View Article at PubMed) PMID:23636173
DOI: Full-text: DOI:10.1038/ki.2013.149

Although the role of the erythropoietin (EPO) receptor (EpoR) in erythropoiesis has been known for decades, its role in nonhematopoietic tissues is still not well defined. Klotho has been shown and EPo has been suggested to protect against acute ischemia-reperfusion injury in the kidney. Here we found in rat kidney and in a rat renal tubular epithelial cell line (NRK cells) EpoR transcript and antigen, and EpoR activity signified as EPo-induced phosphorylation of Jak2, ErK, Akt, and Stat5 indicating the presence of functional EpoR. Transgenic overexpression of Klotho or addition of exogenous recombinant Klotho increased kidney EpoR protein and transcript. In NRK cells, Klotho increased EpoR protein, enhanced EPo-triggered phosphorylation of Jak2 and Stat5, the nuclear translocation of phospho-Stat5, and protected NRK cells from hydrogen peroxide cytotoxicity. Knockdown of endogenous EpoR rendered NRK cells more vulnerable, and overexpression of EpoR more resistant to peroxide-induced cytotoxicity, indicating that EpoR mitigates oxidative damage. Knockdown of EpoR by siRNA abolished Epo-induced Jak2, and Stat5 phosphorylation, and blunted the protective effect of Klotho against peroxide-induced cytotoxicity. Thus in the kidney, EpoR and its activity are downstream effectors of Klotho enabling it to function as a cytoprotective protein against oxidative injury.

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RGD Object Information
RGD ID: 10401070
Created: 2015-09-23
Species: All species
Last Modified: 2015-09-23
Status: ACTIVE



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