Related Experiment Video
Updated: Jan 12, 2026
Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
FGF21-FGFR1 signaling protects against cardiac hypertrophy by regulating PINK1-mediated mitophagy pathway
Lei Chen1, Lingxin Zheng2, Yuan Qin3
1Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China; Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Department of Blood Transfusion, The First Affiliated Hospital (Southwest Hospital) of Army Medical University, Chongqing 400038, China.
Insights
Fibroblast growth factor 21 (FGF21) enhances mitophagy to protect against cardiac hypertrophy. Impaired fibroblast growth factor receptor 1 (FGFR1) expression may limit FGF21
Area of Science:
- Cardiovascular Biology
- Mitochondrial Biology
- Molecular Cardiology
Background:
- Cardiac hypertrophy is a major risk factor for heart failure (HF).
- Mitochondrial dysfunction is central to the progression from cardiac hypertrophy to HF.
- Fibroblast growth factor 21 (FGF21) shows cardioprotective potential but its mechanism in hypertrophic mitochondria is unclear.
Purpose of the Study:
- To investigate the role of FGF21 in cardiac hypertrophy.
- To elucidate the mechanism of FGF21's cardioprotection via mitophagy enhancement.
Main Methods:
- Utilized transverse aortic constriction (TAC) and phenylephrine (PE) models for cardiac hypertrophy.
- Employed FGF21 knockout/knockdown and treatments with P62-mediated mitophagy inducer (PMI) and rapamycin (Rapa).
- Assessed cardiac function, mitochondrial integrity, and mitophagy markers, including PTEN-induced putative kinase 1 (PINK1) and fibroblast growth factor receptor 1 (FGFR1).
Main Results:
- FGF21 deficiency exacerbated cardiac dysfunction, mitochondrial damage, and mitophagy impairment in TAC and PE models.
- FGF21 treatment promoted mitophagy, dependent on PINK1, and improved cardiac function.
- FGFR1 expression was inversely correlated with FGF21 in heart failure, and FGFR1 knockdown inhibited FGF21-mediated mitophagy.
Conclusions:
- FGF21 promotes PINK1-mediated mitophagy, offering a protective effect against cardiac hypertrophy.
- Mismatched FGFR1 expression may impede the beneficial effects of FGF21 in cardiac hypertrophy.
Introduction:
Cardiac hypertrophy is an independent risk factor and the primary predictor of heart failure (HF). Mitochondria are crucial for the shift from hypertrophy to heart failure. The expression of fibroblast growth factor 21 (FGF21), a cardioprotective factor, is increased in patients with cardiac hypertrophy but fails to prevent heart failure. Additionally, the molecular mechanism through which FGF21 exerts its beneficial effects on hypertrophic myocardial mitochondria remains unclear.
Objectives:
Our study investigated the effect of FGF21 on cardiac hypertrophy, elucidating its mechanism of action through the enhancement of mitophagy-mediated cardioprotection.
Methods:
A transverse aortic constriction (TAC) model and a phenylephrine (PE) model were applied to explore the effect and mechanism of FGF21. P62-mediated mitophagy inducer (PMI) and rapamycin (Rapa) were used to confirm that FGF21-regulated mitophagy under overload pressure conditions.
Results:
FGF21 knockout markedly exacerbated TAC-induced cardiac function damage, mitochondrial damage, and mitophagy impairment. In vitro, FGF21 knockdown aggravated PE-induced cardiomyocyte hypertrophy and mitophagy dysfunction. FGF21 treatment promoted mitophagy in the TAC and PE models, but this effect was abolished in the absence of PTEN-induced putative kinase 1 (PINK1). The increase in PINK1 expression induced by Rapa can rescue impaired cardiac function and mitophagy impairment in FGF21-deficient TAC mice. Similarly, PMI enhances mitophagy, which inhibits damage to cardiac functions. A further study revealed that the expression of fibroblast growth factor receptor 1 (FGFR1) and FGF21 was opposite in heart failure. Knockdown of FGFR1 inhibited FGF21-mediated mitophagy.
Conclusion:
FGF21 promotes PINK1-mediated mitophagy to attenuate cardiac hypertrophy, and mismatched FGFR1 expression may hamper the beneficial effect of FGF21 on cardiac hypertrophy.
Related Concept Videos
01:16TGF - β Signaling Pathway
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:24Regulation of Angiogenesis and Blood Supply
01:07MAPK Signaling Cascades