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mTOR Inhibition improves anaemia and reduces organ damage in a murine model of sickle cell disease
| Content Provider | Scilit |
|---|---|
| Author | Wang, Jintao Tran, Jennifer Wang, Hui Guo, Chiao Harro, David Campbell, Andrew D. Eitzman, Daniel T. |
| Copyright Year | 2016 |
| Description | Journal: British Journal of Haematology Mechanistic target of rapamycin (mTOR) has been shown to play an important role in red blood cell physiology, with inhibition of mTOR signalling leading to alterations in erythropoiesis. To determine if mTOR inhibition would improve anaemia in sickle cell disease (SCD), mice with SCD were treated with the dual mTORC1/2 inhibitor, INK128. One week after daily oral drug treatment, erythrocyte count, haemoglobin, and haematocrit were all significantly increased while reticulocyte counts were reduced. These parameters remained stable during 3 weeks of treatment. Similar effects were observed following oral treatment with the mTORC1 inhibitor, sirolimus. Sirolimus treatment prolonged the lifespan of sickle cell erythrocytes in circulation, reduced spleen size, and reduced renal and hepatic iron accumulation in SCD mice. Following middle cerebral artery occlusion, stroke size was reduced in SCD mice treated with sirolimus. In conclusion, mTOR inhibition is protective against anaemia and organ damage in a murine model of SCD. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959967/pdf |
| Ending Page | 469 |
| Page Count | 9 |
| Starting Page | 461 |
| e-ISSN | 13652141 |
| DOI | 10.1111/bjh.14057 |
| Journal | British Journal of Haematology |
| Issue Number | 3 |
| Volume Number | 174 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2016-03-31 |
| Access Restriction | Open |
| Subject Keyword | Journal: British Journal of Haematology Mechanistic Target of Rapamycin Sickle Cell Disease |
| Content Type | Text |
| Resource Type | Article |
