Related Experiment Video
Updated: Sep 28, 2025
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
FGF6 promotes cardiac repair after myocardial infarction by inhibiting the Hippo pathway
Zhicheng Hu1,2, Peng Chen1, Linlin Wang3
1Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, P.R. China.
Insights
Fibroblast growth factor 6 (FGF6) promotes cardiac repair after myocardial infarction (MI) by inhibiting the Hippo pathway. This enhances cardiomyocyte proliferation and improves heart function following ischemic injury.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Molecular Signaling
Background:
- Myocardial infarction (MI) is a leading cause of mortality in coronary artery disease patients.
- Current treatments for MI primarily focus on reducing myocardial cell death, with limited capacity for cell replacement.
- The Hippo pathway plays a critical role in regulating organ size and cell proliferation.
Purpose of the Study:
- To investigate the role of fibroblast growth factor 6 (FGF6) in promoting cardiomyocyte (CM) proliferation after ischemic injury.
- To elucidate the mechanism by which FGF6 influences the Hippo pathway in the context of MI.
- To assess the therapeutic potential of FGF6 in improving cardiac function post-MI.
Main Methods:
- FGF6 protein expression was analyzed in a mouse model of MI.
- The Hippo pathway activation and CM proliferation were examined in ischemic CMs treated with FGF6 or FGF6 sh-RNA.
- Immunofluorescence staining and western blotting were used to assess FGF6's interaction with the Hippo pathway.
Main Results:
- FGF6 expression was significantly upregulated in the MI mouse model.
- FGF6 treatment improved heart function, reduced infarct size, and promoted cardiac repair post-MI.
- FGF6 inhibited the Hippo pathway, leading to YAP nuclear accumulation, an effect mediated by ERK1/2 signaling.
Conclusions:
- FGF6 plays a protective role in cardiac repair following MI.
- FGF6 inhibits the Hippo pathway through ERK1/2, facilitating YAP nuclear translocation and promoting CM proliferation.
- FGF6 represents a potential therapeutic target for enhancing cardiac regeneration after myocardial infarction.
Objectives:
Myocardial infarction (MI) commonly occurs in patients with coronary artery disease and have high mortality. Current clinical strategies for MI still limited to reducing the death of myocardial cells but failed to replace these cells. This study aimed to investigate the role of fibroblast growth factor 6 (FGF6) in enhancing the proliferative potential of cardiomyocytes (CMs) after ischemic injury via the Hippo pathway.
Materials And Methods:
Expression of FGF6 protein was analysed in mice with MI induced by ligation of the left anterior descending coronary artery. Activation of the Hippo pathway and the proliferation potential were examined in ischemic CMs, treated with FGF6 protein or transfected with an adeno-virus carrying FGF6 sh-RNA. Immunofluorescence staining and western blotting were performed to assess the relationship between FGF6 and the Hippo pathway.
Results:
We found that FGF6 expression was significantly increased in the MI mouse model. Knockdown of FGF6 synthesis resulted in poorer heart function after MI. By contrast, treatment with recombinant human FGF6 protein improved heart function, reduced infarct size, and promoted cardiac repair. Additionally, FGF6 restrains the activation of the Hippo pathway and subsequently promotes nuclear accumulation of YAP. This was largely counteracted by treatment with extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126.
Conclusion:
FGF6 inhibits the Hippo pathway via ERK1/2, and facilitates nuclear translocation of YAP, and thereby promotes cardiac repair after MI.
