A research team led by Prof. YANG Huang-Tian from the Shanghai Institute of Nutrition and Health (SINH) of the Chinese Academy of Sciences (CAS), published a research article entitled "IGFBP7 promotes healing of infarcted hearts via suppression of cardiomyocyte necroptosis" in Science China Life Sciences on August 7, 2026.

This study revealed the critical role and novel mechanism of insulin-like growth factor-binding protein 7 (IGFBP7) in suppressing cardiomyocyte necroptosis and promoting cardiac repair following myocardial infarction (MI).

The massive loss of cardiomyocytes following acute MI is a key mechanism leading to ventricular remodeling and heart failure. Previous studies have shown that cardiomyocyte necroptosis plays a critical role in MI-induced cardiomyocyte death, with receptor-interacting protein 3 (RIP3) serving as a key determinant of this process. However, the regulatory mechanisms of RIP3 levels in cardiomyocytes post-MI have not been fully elucidated, and identifying endogenous inhibitory proteins targeting cardiomyocyte necroptosis represents an important direction for the treatment of ischemic heart disease.

The research team led by Prof. Yang found that IGFBP7 expression was significantly elevated in a mouse MI model, reaching a peak at 7 days post-MI.

To explore its function, the researchers generated a cardiomyocyte-specific IGFBP7 knockout (Igfbp7^CM-/-) mouse model. They discovered that the cardiomyocyte-specific deficiency of IGFBP7 exacerbated MI-induced cardiomyocyte necroptosis, cardiac functional worsening, and scar formation. Conversely, the injection of human recombinant IGFBP7 (hIGFBP7) protected infarcted mice hearts and oxygen-glucose deprivation (OGD)-injured murine and human cardiomyocytes via an IGF-independent pathway.

Mechanistically, IGFBP7 interacts with RACK1 protein and promotes its degradation, which disrupts the RACK1-mediated stabilization of Rip3 mRNA, accelerates Rip3 mRNA degradation, and subsequently inhibits the MI-induced upregulation of RIP3. The use of a Rip3 knockout mouse MI model further confirmed the mechanism by which IGFBP7 effectively inhibits necroptosis in injured cardiomyocytes by targeting RIP3.

This study revealed, for the first time, the anti-necroptotic and reparative roles of IGFBP7 in injured cardiomyocytes and infarcted hearts. The research not only broadens the understanding of post-transcriptional regulatory mechanisms of cardiomyocyte necroptosis but also provides a new theoretical basis and potential therapeutic strategy for treating ischemic heart disease by utilizing a natural protein to target and regulate Rip3 mRNA stability.

Prof. YANG Huang-Tian is the corresponding author, and Dr. LI Qiang is the first author of the article. This research was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, and the Research Funding from Hubei Key Laboratory of Embryonic Stem Cell Research.

Schematic model of IGFBP7 suppressing cardiomyocyte necroptosis and promoting cardiac repair post-MI. (Image by Prof. Yang’s group)

Paper link: http://engine.scichina.com/doi/10.1007/s11427-026-3417-2

Scientific Contact:
Prof. YANG Huang-TIan
Shanghai Institute of Nutrition and Health,
Chinese Academy of Sciences
Email: htyang@sinh.ac.cn

Media Contact:
WANG Jin
Shanghai Institute of Nutrition and Health,
Chinese Academy of Sciences
Email: wangjin01@sinh.ac.cn