Impact of systemic erythropoietin deficiency on the lung of mice exposed to hypoxia

Introduction: Erythropoietin (EPO) is well known for its role in erythropoiesis. However, studies from our group and other demonstrated that EPO can also exert protective effects (ie anti-oxidant, anti-inflammatory and anti-apoptotic) in various organs such as heart and brain. Interestingly the expression of EPO and its receptor (EPO-R) has been observed in the lung. Aims and objectives: Our aim is to characterize in the lung, the impact of an EPO systemic deficiency in control condition and in mice exposed to hypoxia. Methods: EPO deficient male mice (EpoTAgh) were exposed or not to hypobaric hypoxia during 24h or 10 days (420 mmHg, Altitude≈ 4500m). The lungs were extracted; the left lobe was used for histological analysis (Masson’s Trichrome, imunohistochemistry) and the right one for molecular approach (ELISA, Immunoblotting and qPCR). Expression of oxidative stress, apoptotic, inflammatory and fibrotic markers of EpoTAgh mice were compared to Wild-Type (WT) littermate mice. Results: As compared to WT, we observed in normoxic EpoTAgh mice a slight increase in oxidative stress and apoptosis markers (ie MPO, DCFDA; caspase 3 and BAX /BCL-2 level respectively), IL-8 concentration, E-cadherin and α-SMA expression. In hypoxia we observed a delayed response of EpoTAgh mice for the expression of studied markers. Interestingly, after 10 days, we observed a marked increase in collagen expression and deposition in EpoTAgh. Conclusions: Our study shows a distinct expression of stress-induced markers in the lung of EPO-deficient mice that is worsened after hypoxic exposure. These results led us to suggest that EPO might also have protective effect against lung injury. * Senior authors contributed equally