TAB3 defect induces augmented cardioprotection loss from ischemic injury.

Yang Sheng, Changfu Xu, Wenping Zeng

Cell biology international 2017 Jul

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The transforming growth factor β-activated kinase-binding protein 3 (TAB3) plays a crucial role in modulating cell apoptosis and proliferation in many diseases, including hepatocellular carcinoma, lung cancer, and intracerebral hemorrhage. However, the functional role of TAB3 in the heart is not well reported. In our study, we first investigated the role of TAB3 in ischemia heart diseases. For in vitro studies, cardiomyocytes (CMs) were isolated from both TAB3 knockout (KO) and wild-type (WT) mice, and the apoptosis ratios were tested after a 48-h ischemic stimulation. A proliferation test and tubeformation assay were underwent at normoxia condition. For in vivo studies, the MI model was completed for both TAB3 KO and WT mice. Echocardiography was evaluated at 3 days and 28 days post-MI, whereas the hemodynamics test was performed 28 days post-MI. The histology results of the apoptosis, proliferation of myocardium, neovasculation of microvessels, and infarct zone assessments were determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining, Ki67 immunostaining, α-SMA/CD31 immunostaining, and the Masson-Trichrome method, respectively. Expression changes of the related proteins caused by TAB3 deficiency were confirmed using both quantitative real-time polymerase chain reaction and immunoblotting. Our results indicate that the absence of TAB3 induced more CMs apoptosis, decrease cardiomyocyte proliferation, and weaker angiogenesis in vitro and in vivo. Worse cardiac function and enlarged scar formation were detected in TAB3 KO mice, and increased expression of active-caspase-3 and decreased expression of NF-κB/p65, Akt, Bcl-2/Bax, and VEGF occurred. In summary, our findings indicate that the absence of TAB3 plays a harmful role in ischemic heart disease. © 2017 International Federation for Cell Biology.

Citation

Yang Sheng, Changfu Xu, Wenping Zeng. TAB3 defect induces augmented cardioprotection loss from ischemic injury. Cell biology international. 2017 Jul;41(7):787-797