| First Author | Guo S | Year | 2013 |
| Journal | J Clin Invest | Volume | 123 |
| Issue | 4 | Pages | 1531-41 |
| PubMed ID | 23524968 | Mgi Jnum | J:197624 |
| Mgi Id | MGI:5494195 | Doi | 10.1172/JCI66969 |
| Citation | Guo S, et al. (2013) Reducing TMPRSS6 ameliorates hemochromatosis and beta-thalassemia in mice. J Clin Invest 123(4):1531-41 |
| abstractText | beta-Thalassemia and HFE-related hemochromatosis are 2 of the most frequently inherited disorders worldwide. Both disorders are characterized by low levels of hepcidin (HAMP), the hormone that regulates iron absorption. As a consequence, patients affected by these disorders exhibit iron overload, which is the main cause of morbidity and mortality. HAMP expression is controlled by activation of the SMAD1,5,8/SMAD4 complex. TMPRSS6 is a serine protease that reduces SMAD activation and blocks HAMP expression. We identified second generation antisense oligonucleotides (ASOs) targeting mouse Tmprss6. ASO treatment in mice affected by hemochromatosis (Hfe(-/-)) significantly decreased serum iron, transferrin saturation and liver iron accumulation. Furthermore, ASO treatment of mice affected by beta-thalassemia (HBB(th3/+) mice, referred to hereafter as th3/+ mice) decreased the formation of insoluble membrane-bound globins, ROS, and apoptosis, and improved anemia. These animals also exhibited lower erythropoietin levels, a significant amelioration of ineffective erythropoiesis (IE) and splenomegaly, and an increase in total hemoglobin levels. These data suggest that ASOs targeting Tmprss6 could be beneficial in individuals with hemochromatosis, beta-thalassemia, and related disorders. |
