| First Author | Ghosh MC | Year | 2013 |
| Journal | Cell Metab | Volume | 17 |
| Issue | 2 | Pages | 271-81 |
| PubMed ID | 23395173 | Mgi Jnum | J:198050 |
| Mgi Id | MGI:5495339 | Doi | 10.1016/j.cmet.2012.12.016 |
| Citation | Ghosh MC, et al. (2013) Deletion of iron regulatory protein 1 causes polycythemia and pulmonary hypertension in mice through translational derepression of HIF2alpha. Cell Metab 17(2):271-81 |
| abstractText | Iron regulatory proteins (Irps) 1 and 2 posttranscriptionally control the expression of transcripts that contain iron-responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor, and hypoxia-inducible factor 2alpha (HIF2alpha). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low-iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2alpha protein expression in kidneys of Irp1(-/-) mice, which led to increased erythropoietin (EPO) expression, polycythemia, and concomitant tissue iron deficiency. Increased HIF2alpha expression in pulmonary endothelial cells induced high expression of endothelin-1, likely contributing to the pulmonary hypertension of Irp1(-/-) mice. Our results reveal why anemia is an early physiological consequence of iron deficiency, highlight the physiological significance of Irp1 in regulating erythropoiesis and iron distribution, and provide important insights into the molecular pathogenesis of pulmonary hypertension. |
