Cardiac-specific Traf2 overexpression enhances cardiac hypertrophy through activating AKT/GSK3β signaling

Huang, Yinqing; Wu, Dengyin; Zhang, Xin; Jiang, Minghua; Hu, Chaohui; Lin, Jia Chun; Tang, Jiang; Wu, Lianpin

doi:10.1016/j.gene.2013.12.052

Cited by 30 publications

(27 citation statements)

References 23 publications

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“…Previous study has found that GSK-3β activation was involved in the process of cardiac hypertrophy (Chen et al, 2018). For example, previous research has found that overexpressed cardiac-specific Traf2 enhances cardiac hypertrophy by activating AKT/GSK3β signaling pathway (Huang et al, 2014). In addition, cardiacspecific mindin overexpression attenuates cardiac hypertrophy by blocking AKT/GSK3β and TGF-β1-Smad signaling (Yan et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Inhibiting SLC26A4 reverses cardiac hypertrophy in H9C2 cells and in rats

Tang

Zheng

et al. 2020

PeerJ

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Background It has been confirmed that mutations in solute carrier family 26 member 4 (SLC26A4) contribute to pendred syndrome. However, the role of SLC26A4 in cardiac hypertrophy and the signaling pathways remain unclear. Methods Cardiomyocytes were treated by 200 µM phenylephrine (PE) to induce cardiac hypertrophy. Also, the expression of SLC26A4, GSK3, cardiac hypertrophy markers including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was detected through real-time quantitative polymerase chain reaction (RT-qPCR). Flow cytometry assay was used to test the apoptosis of PE-induced cardiomyocytes transfected by small interfere RNA (siRNA)-SLC26A4. Furthermore, we detected the expression of autophagy-related markers including light chain 3 (LC3) and P62. Finally, we established a rat model of abdominal aortic constriction (AAC)-induced cardiac hypertrophy in vivo. Results RT-qPCR results showed that the mRNA expression of SLC26A4 was significantly up-regulated in PE-induced cardiac hypertrophy. After inhibiting SLC26A4, the release of ANP and BNP was significantly decreased and GSK3β was elevated in vivo and in vitro. Furthermore, inhibiting SLC26A4 promoted apoptosis of cardiac hypertrophy cells. In addition, LC3 was down-regulated and P62 was enhanced after transfection of siRNA-SLC26A4. Conclusion Our findings revealed that SLC26A4 increases cardiac hypertrophy, and inhibiting SLC26A4 could decrease the release of ANP/BNP and promote the expression of GSK-3β in vitro and in vivo. Moreover, SLC26A4 silencing inhibits autophagy of cardiomyocytes and induces apoptosis of cardiomyocytes. Therefore, SLC26A4 possesses potential value to be a therapeutic target of cardiac hypertrophy, and our study provides new insights into the mechanisms of cardiac hypertrophy.

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Section: Discussionmentioning

confidence: 99%

Inhibiting SLC26A4 reverses cardiac hypertrophy in H9C2 cells and in rats

Tang

Zheng

et al. 2020

PeerJ

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“…[57][58][59] Knockdown of Akt by small interfering RNA blunts agonist-dependent hypertrophy, whereas in vivo cardiacspecific expression of Akt causes a brief phase of cardiac hypertrophy, Autophagy in spontaneously hypertensive rats W Wang et al followed by chamber dilation and impaired systolic function and death. 60,61 In hypertrophic cardiomyocytes, one major event is increased protein turnover, where enhanced protein synthesis is accompanied by increased removal of deleterious proteins. Many pathways that mediate protein turnover depend on mTOR.…”

Section: Discussionmentioning

confidence: 99%

Augmentation of autophagy by atorvastatin via Akt/mTOR pathway in spontaneously hypertensive rats

Wang

Qian

et al. 2015

Hypertens Res

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Autophagy is activated in hypertension-induced cardiac hypertrophy. However, the mechanisms and significance of an activated autophagy are not clear. This study was designed to determine the role of atorvastatin (ATO) in cardiac autophagy and associated benefits on cardiac remodeling and left ventricular function in spontaneously hypertensive rats (SHRs). Twenty-eight male SHRs at 8 weeks of age were randomized to treatment with vehicle (saline solution; SHR+V) or ATO (SHR+ATO; 50 mg kg(-1) per day) for 6 or 12 months. Age-matched male Wistar-Kyoto (WKY) rats were used as normotensive controls. Cardiac magnetic resonance was used to evaluate cardiac function and structure. Compared with WKY rats, SHRs showed significant left ventricle (LV) dysfunction, remodeling and increases in cardiomyocyte size, which were all attenuated by 6 and 12 months of ATO treatment. Compared with WKY rats, autophagy was activated in the hearts of SHRs and this effect was amplified by chronic ATO treatment, particularly following 12 months of treatment. Protein expression levels of microtubule-associated protein-1 light chain 3-II and beclin-1, the biomarkers of an activated cardiac autophagy, were significantly elevated in ATO-treated versus vehicle-treated SHRs and control WKY rats. Cardiac Akt and phosphorylated mammalian target of rapamycin (mTOR) expression were also increased in the hearts of SHR versus WKY rats, and this effect was attenuated by ATO treatment. These findings suggest that ATO-mediated improvements in LV function and structure in SHRs may be, in part, through its regulation of cardiac autophagy via the Akt/mTOR pathway.

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“…Likewise, the TNF-␣ inhibitor etanercept blocks ANG II-dependent activation of p38MAPK and JNK (990). TRAF2 is a required component for TNF-␣ induced downstream signaling, and in vitro analysis indicates that TRAF2 enhances ANG IIdependent upregulation in cardiomyocyte area and ANP/ BNP expression through Akt activation and subsequent inhibition of GSK3␤ activation (405). G) IMMUNOPROTEASOME.…”

Section: Ang II In Cardiac Hypertrophymentioning

confidence: 99%

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

735

776

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The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG II) type 1 receptor (ATR) is believed to mediate most functions of ANG II in the system. ATR utilizes various signal transduction cascades causing hypertension, cardiovascular remodeling, and end organ damage. Moreover, functional cross-talk between ATR signaling pathways and other signaling pathways have been recognized. Accumulating evidence reveals the complexity of ANG II signal transduction in pathophysiology of the vasculature, heart, kidney, and brain, as well as several pathophysiological features, including inflammation, metabolic dysfunction, and aging. In this review, we provide a comprehensive update of the ANG II receptor signaling events and their functional significances for potential translation into therapeutic strategies. ATR remains central to the system in mediating physiological and pathophysiological functions of ANG II, and participation of specific signaling pathways becomes much clearer. There are still certain limitations and many controversies, and several noteworthy new concepts require further support. However, it is expected that rigorous translational research of the ANG II signaling pathways including those in large animals and humans will contribute to establishing effective new therapies against various diseases.

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Cardiac-specific Traf2 overexpression enhances cardiac hypertrophy through activating AKT/GSK3β signaling

Cited by 30 publications

References 23 publications

Inhibiting SLC26A4 reverses cardiac hypertrophy in H9C2 cells and in rats

Inhibiting SLC26A4 reverses cardiac hypertrophy in H9C2 cells and in rats

Augmentation of autophagy by atorvastatin via Akt/mTOR pathway in spontaneously hypertensive rats

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

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