| First Author | Ma S | Year | 2021 |
| Journal | Cell | Volume | 184 |
| Issue | 4 | Pages | 969-982.e13 |
| PubMed ID | 33571427 | Mgi Jnum | J:304427 |
| Mgi Id | MGI:6508472 | Doi | 10.1016/j.cell.2021.01.024 |
| Citation | Ma S, et al. (2021) A role of PIEZO1 in iron metabolism in mice and humans. Cell 184(4):969-982.e13 |
| abstractText | Iron overload causes progressive organ damage and is associated with arthritis, liver damage, and heart failure. Elevated iron levels are present in 1%-5% of individuals; however, iron overload is undermonitored and underdiagnosed. Genetic factors affecting iron homeostasis are emerging. Individuals with hereditary xerocytosis, a rare disorder with gain-of-function (GOF) mutations in mechanosensitive PIEZO1 ion channel, develop age-onset iron overload. We show that constitutive or macrophage expression of a GOF Piezo1 allele in mice disrupts levels of the iron regulator hepcidin and causes iron overload. We further show that PIEZO1 is a key regulator of macrophage phagocytic activity and subsequent erythrocyte turnover. Strikingly, we find that E756del, a mild GOF PIEZO1 allele present in one-third of individuals of African descent, is strongly associated with increased plasma iron. Our study links macrophage mechanotransduction to iron metabolism and identifies a genetic risk factor for increased iron levels in African Americans. |
