Key result
FoxO1 overexpression upregulated the TLR4/NF-κB signaling pathway to promote cardiomyocyte apoptosis and inflammatory injury in CVB3-induced viral myocarditis, an effect reversed by TLR4 silencing.
Why the study?
To investigate the effect of FoxO on CVB3-induced cardiomyocyte inflammation and apoptosis via modulation of the TLR4/NF-κB signaling pathway.
FoxO1 promotes cardiomyocyte apoptosis and inflammation in viral myocarditis by upregulating the TLR4/NF-κB signaling pathway, suggesting a potential therapeutic target.
FoxO1 promotes CVB3-induced cardiomyocyte injury via TLR4/NF-κB in animal models; leaves open therapeutic targeting in viral myocarditis.
To investigate the possible effect of FoxO on coxsackievirus B3 (CVB3) -induced cardiomyocyte inflammation and apoptosis via modulation of the TLR4/NF-κB signaling pathway.Viral myocarditis (VMC) models were establied via CVB3 infection both in vivo and in vitro. Western blotting was adopted to detect FoxO1 and TLR4 expressions in myocardial tissues and cells. Cardiomyocytes of suckling mouse were divided into the control, CVB3, CVB3 + pcDNA, CVB3 + pcDNA-FoxO1, CVB3 + TLR4 siRNA, and CVB3 + pcDNA-FoxO1 + TLR4 siRNA groups. Flow cytometry was employed to evaluate cell apoptosis. The expressions of inflammatory factors including TNF-α, IL-1β, and IL-6 were detected via quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Then, TLR4/NF-κB pathway-related proteins were determined via Western blotting.VMC mice had increased FoxO1 and TLR4 expressions in myocardial tissues. Cardiomyocytes with CVB3 infection also had upregulated protein expressions of p-FoxO1/FoxO1 and TLR4. Compared with those in the control group, the cardiomyocytes in the CVB3 group were increased in LDH and CK-MB levels, cell apoptosis rate and inflammatory factors (TNF-α, IL-1β and IL-6), as well as protein expressions of TLR4 and p-p65/p65. Compared with those in the CVB3 group, the cardiomyocytes in the CVB3 + pcDNA-FoxO1 group were further upregulated whereas those in the CVB3 +TLR4 siRNA group were downregulated in the aforementioned indicators. Furthermore, TLR4 siRNA can reverse the effect of pcDNA-FoxO1 on the aggravation of cardiomyocyte injury induced by CVB3 infection.FoxO1 can upregulate the TLR4/NF-κB signaling pathway to promote cardiomyocyte apoptosis and inflammatory injury in CVB3-induced VMC.
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Tao et al. (2023) studied Viral myocarditis. FoxO1 modulation (pcDNA-FoxO1 and TLR4 siRNA) vs. Control and CVB3-only infected groups was evaluated on Cardiomyocyte apoptosis and inflammatory factor levels (TNF-α, IL-1β, IL-6) (p=<0.05). FoxO1 overexpression upregulated the TLR4/NF-κB signaling pathway to promote cardiomyocyte apoptosis and inflammatory injury in CVB3-induced viral myocarditis, an effect reversed by TLR4 silencing.
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