Abstract
The RasGAP SH3 domain-binding proteins (G3BPs) are a family of RNA-binding proteins that can co-ordinate signal transduction and post-transcriptional gene regulation. G3BPs have been shown to be involved in mediating a great diversity of cellular processes such as cell survival, growth, proliferation and apoptosis. But the potential roles of G3BPs in the pathogenesis and progression of cardiovascular diseases remain to be clarified. In the present study, we provide the first evidence that suggests the participation of G3BP2 in cardiac hypertrophy. In cultured neonatal rat cardiomyocytes (NRCMs), treatment with isoproterenol (ISO, 0.1–100 μmol/L) significantly elevated the mRNA and protein levels of G3BP2. Similar results were observed in the hearts of rats subjected to 7D-injection of ISO, accompanied by obvious heart hypertrophy and elevated the expression of hypertrophy marker genes ANF, BNP and β-MHC in heart tissues. Overexpression of G3BP2 in NRCMs led to hypertrophic responses evidenced by increased cellular surface area and the expression of hypertrophy marker genes, whereas knockdown of G3BP2 significantly attenuated ISO-induced hypertrophy of NRCMs. We further showed that G3BP2 directly interacted with IκBα and promoted the aggregation of the NF-κB subunit p65 in the nucleus and increased NF-κB-dependent transcriptional activity. NF-κB inhibition with PDTC (50 μmol/L) or p65 knockdown significantly decreased the hypertrophic responses in NRCMs induced by ISO or G3BP2 overexpression. These results give new insight into the functions of G3BP2 and may help further elucidate the molecular mechanisms underlying cardiac hypertrophy.
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Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (No 81072641, 81273499, 81473205, 81400359, 81673433, and 81200096), the Team item of the Natural Science Foundation of Guangdong Province (No S2011030003190), the Major Project of Guangdong Provincial Department of Science and Technology (No 2013B090700010), the Major Project of Platform Construction Education Department of Guangdong Province (No 2014GKPT002), and the Special Program for Applied Science and Technology of Guangdong Province (No 2015B020232009).
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Hong, Hq., Lu, J., Fang, Xl. et al. G3BP2 is involved in isoproterenol-induced cardiac hypertrophy through activating the NF-κB signaling pathway. Acta Pharmacol Sin 39, 184–194 (2018). https://doi.org/10.1038/aps.2017.58
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DOI: https://doi.org/10.1038/aps.2017.58
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