美国霍华德·休斯医学研究所Ardem Patapoutian团队发现，PIEZO1可在小鼠和人类的铁代谢中发挥作用。这一研究成果发表在2021年2月18日出版的国际学术期刊《细胞》上。

研究人员表示，铁过量会导致进行性器官损伤，并伴有关节炎、肝损伤和心力衰竭。1％–5％的人体内铁水平升高；但是，铁过量的监测和诊断不足。影响体内铁平衡的遗传因素也逐渐被发现。具有遗传性干瘪细胞增多症（一种在机械敏感的PIEZO1离子通道中具有功能获得（GOF）突变的罕见疾病）的个体会随着年龄的增加出现铁过量。

研究人员发现，GOF Piezo1等位基因在小鼠中的组成型表达或巨噬细胞表达能够破坏铁调节因子铁调素的水平，并导致铁过量。研究人员进一步表明，PIEZO1是巨噬细胞吞噬活性和红细胞更新的关键调节因子。令人惊讶的是，研究人员发现，E756del是存在于三分之一非洲血统人群中的轻度GOF PIEZO1等位基因，并与血浆铁含量增加密切相关。

这项研究将巨噬细胞机械转导与铁代谢联系起来，并确定了非裔美国人铁水平升高的遗传危险因素。 

附：英文原文

Title: A role of PIEZO1 in iron metabolism in mice and humans

Author: Shang Ma, Adrienne E. Dubin, Yunxiao Zhang, Seyed Ali Reza Mousavi, Yu Wang, Adam M. Coombs, Meaghan Loud, Immacolata Andolfo, Ardem Patapoutian

Issue&Volume: 2021/02/18

Abstract: 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.

DOI: 10.1016/j.cell.2021.01.024

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00067-2