2. Academic Validation
  3. Omentin-1 drives cardiomyocyte cell cycle arrest and metabolic maturation by interacting with BMP7

Omentin-1 drives cardiomyocyte cell cycle arrest and metabolic maturation by interacting with BMP7

  • Cell Mol Life Sci. 2023 Jun 21;80(7):186. doi: 10.1007/s00018-023-04829-1.
Huijun Yang # 1 2 3,  Shen Song # 2,  Jiacheng Li 4,  Yandong Li 2,  Jie Feng 2,  Quan Sun 1 5,  Xueting Qiu 1 5,  Ziwei Chen 2,  Xue Bai 2,  Xinchang Liu 2,  Hong Lian 2,  Lihui Liu 2,  Yongping Bai 6 7,  Guogang Zhang 8 9,  Yu Nie 10 11 12
Affiliations

Affiliations

  • 1 Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China.
  • 2 State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Street, Beilishi Road, Xicheng District, Beijing, 100037, People's Republic of China.
  • 3 Department of Cardiovascular Medicine, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, China.
  • 4 Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
  • 5 Department of Geriatric Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Street, Xiangya Road, Kaifu District, Changsha, 410008, People's Republic of China.
  • 6 Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China. baiyongping@csu.edu.cn.
  • 7 Department of Geriatric Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Street, Xiangya Road, Kaifu District, Changsha, 410008, People's Republic of China. baiyongping@csu.edu.cn.
  • 8 Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China. zhangguogang@csu.edu.cn.
  • 9 Department of Geriatric Medicine, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 87 Street, Xiangya Road, Kaifu District, Changsha, 410008, People's Republic of China. zhangguogang@csu.edu.cn.
  • 10 State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Street, Beilishi Road, Xicheng District, Beijing, 100037, People's Republic of China. nieyu@fuwaihospital.org.
  • 11 Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, 518057, China. nieyu@fuwaihospital.org.
  • 12 National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Fuwai Central-China Hospital, Central China Branch of National Center for Cardiovascular Diseases, Zhengzhou, 450046, China. nieyu@fuwaihospital.org.
  • # Contributed equally.
PMID: 37344704 DOI: 10.1007/s00018-023-04829-1
Abstract

Mammalian cardiomyocytes (CMs) undergo maturation during postnatal heart development to meet the increased demands of growth. Here, we found that omentin-1, an adipokine, facilitates CM cell cycle arrest and metabolic maturation. Deletion of omentin-1 causes mouse heart enlargement and dysfunction in adulthood and CM maturation retardation in juveniles, including delayed cell cycle arrest and reduced fatty acid oxidation. Through RNA Sequencing, molecular docking analysis, and proximity ligation assays, we found that omentin-1 regulates CM maturation by interacting directly with bone morphogenetic protein 7 (BMP7). Omentin-1 prevents BMP7 from binding to activin type II receptor B (ActRIIB), subsequently decreasing the downstream pathways mothers against DPP homolog 1 (SMAD1)/Yes-associated protein (YAP) and p38 mitogen-activated protein kinase (p38 MAPK). In addition, omentin-1 is required and sufficient for the maturation of human embryonic stem cell-derived CMs. Together, our findings reveal that omentin-1 is a pro-maturation factor for CMs that is essential for postnatal heart development and cardiac function maintenance.

Keywords

BMP7; Cardiomyocyte; Cell cycle arrest; Cell metabolism; Omentin-1; Postnatal heart development; hES-CMs.

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