上海海洋大学陈良标团队近期取得重要工作进展，他们研究提出，bmp10通过调节铁稳态维持心脏功能。相关研究成果2024年10月14日在线发表于《遗传学报》杂志上。

据介绍，心脏病仍然是全球死亡的主要原因。铁失衡，无论是缺乏还是超载，都会导致心力衰竭。然而，控制心脏铁稳态的分子机制知之甚少。

研究人员发现，对胚胎心脏发育至关重要的心脏生成形态发生因子bmp10的突变会导致斑马鱼严重贫血和心肌肥大。最初，bmp10缺乏会导致心脏缺铁，后来由于心脏细胞中hepcidin/ferroportin轴失调而进展为铁过载，导致铁死亡和心力衰竭。

在bmp10^-/-突变体中早期补充铁可以挽救红细胞生成，而幼鱼中的铁螯合可以显著减轻心肌肥大。研究人员进一步证明，HIF1α驱动的缺氧信号传导与IL6/p-STAT3炎症途径之间的相互作用对于调节心脏铁代谢至关重要。

总之，这一发现揭示了BMP10是脊椎动物心脏铁稳态的关键调节因子，并强调了靶向BMP10-hepcidin-铁轴作为铁相关心肌病治疗策略的潜力。

附：英文原文

Title: bmp10 maintains cardiac function by regulating iron homeostasis

Author: Liangbiao Chen a b

Issue&Volume: 2024/10/14

Abstract: Heart disease remains the leading cause of death worldwide. Iron imbalance, whether deficiency or overload, contributes to heart failure. However, the molecular mechanisms governing iron homeostasis in the heart are poorly understood. Here, we demonstrate that mutation of bmp10, a heart-born morphogen crucial for embryonic heart development, results in severe anemia and cardiac hypertrophy in zebrafish. Initially, bmp10 deficiency causes cardiac iron deficiency, which later progresses to iron overload due to the dysregulated hepcidin/ferroportin axis in cardiac cells, leading to ferroptosis and heart failure. Early iron supplementation in bmp10/ mutants rescues erythropoiesis, while iron chelation in juvenile fishes significantly alleviates cardiac hypertrophy. We further demonstrate that the interplay between HIF1α-driven hypoxic signaling and the IL6/p-STAT3 inflammatory pathways is critical for regulating cardiac iron metabolism. Our findings reveal BMP10 as a key regulator of iron homeostasis in the vertebrate heart and highlight the potential of targeting the BMP10-hepcidin-iron axis as a therapeutic strategy for iron-related cardiomyopathy.

DOI: 10.1016/j.jgg.2024.10.003

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852724002637