Fig. 3 | Signal Transduction and Targeted Therapy

Fig. 3

From: Exercise training maintains cardiovascular health: signaling pathways involved and potential therapeutics

Fig. 3

The C/EBPβ/CITED4 pathway in exercise-induced physiological cardiac hypertrophy and exercise-induced cardioprotection. Exercise leads to downregulation of the transcription factor C/EBPβ which is associated with increased AKT activity in the heart. The C/EBPβ interacts with SRF binding to the promoters of cardiac genes (e.g., GATA4 and α-MHC) and CITED4, leading to a negative transcriptional regulation of these genes. Increased CITED4 can act as a regulator of mTOR signaling with increased phosphorylation of p70S6K, ULK1/2, and 4E-BP, which mediates the beneficial effects of CITED4 in promoting physiological cardiac hypertrophy and preventing cardiac I/R injury. Increasing CITED4 is also able to prevent pathological hypertrophy through activating the mTOR pathway and upregulating anti-fibrotic miR-30d. C/EBPβ CCAAT/enhancer binding protein β, SRF serum response factor, CITED4 CBP/p300-interacting transactivator with ED-rich carboxyterminal domain 4, α-MHC α-myosin heavy chain, mTOR mammalian target of rapamycin, AKT protein kinase B, miR microRNA, LV left ventricle, CM cardiomyocyte, I/R ischemia-reperfusion

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