Program in Anemia Signaling Research, Division of Nephrology, Program in Membrane Biology, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
INSERM, U1043, CNRS, U5282, Université Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan Toulouse, France.
Front Pharmacol. 2014 May 19;5:114. doi: 10.3389/fphar.2014.00114. eCollection 2014.
Matriptase-2, encoded by the TMPRSS6 gene, is a member of the type II transmembrane serine protease family. Matriptase-2 has structural and enzymatic similarities to matriptase-1, which has been implicated in cancer progression. Matriptase-2 was later established to be essential in iron homeostasis based on the phenotypes of iron-refractory iron deficiency anemia identified in mouse models as well as in human patients with TMPRSS6 mutations. TMPRSS6 is expressed mainly in the liver and negatively regulates the production of hepcidin, the systemic iron regulatory hormone. This review focuses on the current understanding of matriptase-2 biochemistry, and its role in iron metabolism and cancer progression. In light of recent investigations, the function of matriptase-2 in hepcidin regulation, how it is being regulated, as well as the therapeutic potential of matriptase-2 are also discussed.
组织蛋白酶 2 由 TMPRSS6 基因编码，是 II 型跨膜丝氨酸蛋白酶家族的成员。组织蛋白酶 2 在结构和酶学上与已被证实与癌症进展有关的组织蛋白酶 1 相似。后来发现，组织蛋白酶 2 在铁稳态中是必不可少的，这是基于铁难治性缺铁性贫血的表型在小鼠模型中以及 TMPRSS6 突变的人类患者中确定的。TMPRSS6 主要在肝脏中表达，并负调控系统铁调节激素——hepcidin 的产生。这篇综述重点介绍了目前对组织蛋白酶 2 生化特性及其在铁代谢和癌症进展中的作用的理解。鉴于最近的研究，还讨论了组织蛋白酶 2 在 hepcidin 调节中的作用、它是如何被调节的以及组织蛋白酶 2 的治疗潜力。
