An IL-6/STAT3/MR/FGF21 axis mediates heart-liver cross-talk after myocardial infarction-Reference-Cited by-同舟云学术

An IL-6/STAT3/MR/FGF21 axis mediates heart-liver cross-talk after myocardial infarction

Published:2023-04-07 Issue:14 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Sun Jian-Yong¹²^ORCID,Du Lin-Juan¹²^ORCID,Shi Xue-Rui³^ORCID,Zhang Yu-Yao⁴^ORCID,Liu Yuan¹²,Wang Yong-Li³^ORCID,Chen Bo-Yan¹²^ORCID,Liu Ting¹²,Zhu Hong¹²^ORCID,Liu Yan¹²,Ruan Cheng-Chao⁵^ORCID,Gan Zhenji⁶^ORCID,Ying Hao⁷,Yin Zhinan⁸⁹^ORCID,Gao Ping-Jin¹⁰,Yan Xiaoxiang¹¹^ORCID,Li Ruo-Gu³^ORCID,Duan Sheng-Zhong¹²¹²^ORCID

Affiliation:

1. Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China.

2. National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai 200011, China.

3. Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.

4. Department of Medicine, Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.

5. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

6. State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Chemistry and Biomedicine Innovation Center (ChemBIC), Model Animal Research Center, Nanjing University Medical School, Nanjing University, Nanjing 210061, China.

7. CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China.

8. Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, Guangdong, China.

9. The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou 510632, Guangdong, China.

10. Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

11. Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

12. Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Shanghai, China.

Abstract

The liver plays a protective role in myocardial infarction (MI). However, very little is known about the mechanisms. Here, we identify mineralocorticoid receptor (MR) as a pivotal nexus that conveys communications between the liver and the heart during MI. Hepatocyte MR deficiency and MR antagonist spironolactone both improve cardiac repair after MI through regulation on hepatic fibroblast growth factor 21 (FGF21), illustrating an MR/FGF21 axis that underlies the liver-to-heart protection against MI. In addition, an upstreaming acute interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway transmits the heart-to-liver signal to suppress MR expression after MI. Hepatocyte Il6 receptor deficiency and Stat3 deficiency both aggravate cardiac injury through their regulation on the MR/FGF21 axis. Therefore, we have unveiled an IL-6/STAT3/MR/FGF21 signaling axis that mediates heart-liver cross-talk during MI. Targeting the signaling axis and the cross-talk could provide new strategies to treat MI and heart failure.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.ade4110

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