The renal hormone Erythropoietin (Epo) is the principal regulator of erythrocyte production and differentiation. Epo production by the kidney is induced by an insufficient supply of oxygen (hypoxia), e.g. anaemia, to compensate for reduced oxygen capacity of the blood. The adult human kidney is the main source of systemic Epo and kidney cell lines capable of Epo production would provide an interesting model to study the regulation and characteristics of Epo under hypoxia, inflammation etc. However, many groups have shown that transformed carcinoma cells like Renal Clear Carcinoma cell lines (RCCs) are not able to produce any Erythropoietin under hypoxic conditions. Therefore in many studies hepatocellular carcinoma or neuroblastoma cell lines were used to study Epo regulation. This led to the identification of Hypoxia-Inducible Factors (HIF-1 and -2alpha) as well as GATA transcription factors and Hepatic nuclear factor 4alpha (HNF4alpha) as main regulators of Epo gene expression.

Here we present the first Renal Epo Producing Cell line (REPC) which shows Epo regulation under hypoxic conditions and suppression of Epo by cytokines IL-1beta and TNFalpha like in inflammatory anaemia. We studied the involvement of HIF-2alpha and HNF4alpha for Epo expression in REPC in comparison to RCC cells; in addition the involvement of microRNAs and indirect regulators was investigated.