FGF6 promotes cardiac repair after myocardial infarction by inhibiting the Hippo pathway

Abstract

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.

The FGF6 amplification mutation plays an important role in the progression and treatment of malignant meningioma

“…As an important member of the FGF family, FGF6 plays an important role in regulating cell proliferation, cell differentiation, angiogenesis and muscle production [ 30 , 31 ], but overexpressed FGF6 also promotes tumor progression. One study found that the interaction between LINC00265 and miR-4677–3p upregulated the expression of FGF6 to promote the proliferation, invasion and migration of bladder cancer [ 32 ].…”

FGF10 Protects aganist Myocardial Ischemia/Reperfusion Injury through AMPK/mTOR/TFEB Pathway

“…Cellular apoptosis directly contributed to cardiac dysfunction during MIRI. [21,22] Recent studies demonstrated that FGF10 may protect hepatocytes and renal tubular cells against apoptosis after I/R injury, [8,9] suggesting a possible role for FGF10 in the regulation of apoptosis after MIRI. To investigate this, mice were intraperitoneally injected with recombinant human FGF10 (rFGF10) protein (2mg/kg) daily for 2 weeks.…”

FGF10 Protects against Myocardial Ischemia/Reperfusion Injury through AMPK/mTOR/TFEB Pathway

“…Cellular apoptosis directly contributes to cardiac dysfunction upon MIRI [21,22]. Recent studies demonstrated that FGF10 may protect hepatocytes and renal tubular cells against apoptosis after I/R injury [8,9], suggesting it may play a role in the regulation of apoptosis after MIRI.…”