bmp10 maintains cardiac function by regulating iron homeostasis  

作　　者：Ruiqin Hu Genfang Li Peng Hu Hongbo Niu Wenhao Li Shouwen Jiang Guijun Guan Qianghua Xu Mingli Liu Liangbiao Chen 

机构地区：[1]International Research Center for Marine Bioscience(Ministry of Science and Technology),Shanghai Ocean University,Shanghai 201306,China [2]Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources(Ministry of Education)Shanghai Ocean University,Shanghai 201306,China [3]Key Laboratory of Sustainable Exploitation of Oceanic Fisheries Resources,College of Marine Science,Shanghai Ocean University,Shanghai 201306,China

出　　处：《Journal of Genetics and Genomics》2024年第12期1459-1473,共15页遗传学报（英文版）

基　　金：supported by grants from National Natural Science Foundation of China(32130109);National Key Research and Development Program of China(2018YFD0900600)。

摘　　要：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 HIF1adriven 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.

关 键 词：bmp10 IRON ANEMIA INFLAMMATION Ferroptosis Cardiac hypertrophy 

分 类 号：R54[医药卫生—心血管疾病]