TIEG1 deficiency confers enhanced myocardial protection in the infarcted heart by mediating the Pten/Akt signalling pathway

Cen,Mingqiu; Hu,Pengfei; Cai,Zhaobin; Fang,Tianfu; Zhang,Jiancheng; Lu,Ming

doi:10.3892/ijmm.2017.2889

TIEG1 deficiency confers enhanced myocardial protection in the infarcted heart by mediating the Pten/Akt signalling pathway

Authors:
- Mingqiu Cen
- Pengfei Hu
- Zhaobin Cai
- Tianfu Fang
- Jiancheng Zhang
- Ming Lu
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Affiliations: Department of Cardiology, Xixi Hospital of Hangzhou, Hangzhou, Zhejiang 310023, P.R. China, Department of Cardiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China, Department of Emergency Medicine, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China
Published online on: February 13, 2017 https://doi.org/10.3892/ijmm.2017.2889
Pages: 569-578
Copyright: © Cen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The transforming growth factor (TGF)-β-inducible early gene-1 (TIEG1) plays a crucial role in modulating cell apoptosis and proliferation in a number of diseases, including pancreatic cancer, leukaemia and osteoporosis. However, the functional role of TIEG1 in the heart has not been fully defined. In this study, we first investigated the role of TIEG1 in ischaemic heart disease. For in vitro experiments, cardiomyocytes were isolated from both TIEG1 knockout (KO) and wile-type (WT) mice, and the apoptotic ratios were evaluated after a 48‑h ischaemic insult. A cell proliferation assay was performed after 7 days of incubation under normoxic conditions. In addition, the angiogenic capacity of endothelial cells was determined by tube formation assay. For in vivo experiments, a model of myocardial infarction (MI) was established using both TIEG1 KO and WT mice. Echocardiography was performed at 3 and 28 days post-MI, whereas the haemodynamics test was performed 28 days post-MI. Histological analyses of apoptosis, proliferation, angiogenesis and infarct zone assessments were performed using terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL) staining, BrdU immunostaining, α-smooth muscle actin (α-SMA)/CD31 immunostaining and Masson's trichrome staining, respectively. Changes in the expression of related proteins caused by TIEG1 deficiency were confirmed using both reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Our results demonstrated that the absence of TIEG1 prevented cardiomyocytes from undergoing apoptosis and promoted higher proliferation; it stimulated the proliferation of endothelial cells in vitro and in vivo. Improved cardiac function and less scar formation were observed in TIEG1 KO mice, and we also observed the altered expression of phosphatase and tensin homolog (Pten), Akt and Bcl-2/Bax, as well as vascular endothelial growth factor (VEGF). On the whole, our findings indicate that the absence of TIEG1 plays a cardioprotective role in ischaemic heart disease by promoting changes in Pten/Akt signalling.

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