Ad-HGF induces autophagy in hypoxia-injured H9c2 cardiomyocytes via activating NF-kappa B signaling

作者：Liu, Jia-Bao; Wu, Peng; Wang, Yun-Le; Du, Ying-Qiang; A, Nan; Liu, Shui-Yuan; Zhang, Yi-Ming; Zhou, Ning-Tian; Xu, Zhi-Hui; Yang, Zhi-Jian^*

来源：International Journal of Clinical and Experimental Pathology, 2016, 9(10): 10169-+.

• Ad-HGF
• hypoxia
• autophagy
• NF-kappa B
• H9c2 cell

Autophagy at early stage of hypoxia has been demonstrated to play a vital role in protecting myocardium. Increasing evidences suggest that transcription factor NF-kappa B is involved in autophagy. Furthermore, our previous studies have confirmed that adenovirus carrying the HGF gene (Ad-HGF) could protect the heart against myocardial ischemia. However, the relationship among Ad-HGF, autophagy and NF-kappa B signaling in myocardial infarction (MI) is still unknown. Therefore, we aimed to investigate whether Ad-HGF could regulate autophagy through NF-kappa B signaling in an in vitro hypoxia model. Autophagy was observed by transmission electron microscope and Ad-mRFP-GFP-LC3 infection. Protein expression levels of LC3-I, LC3-II, Beclin-1, p62, NF-kappa B p65 and phosphorylated NF-kappa B p65 were analyzed by western blot or immunofluorescence. Notably, we found that autophagy in H9c2 cells enhanced at early stage after hypoxia. Ad-HGF treatment dose-dependently promoted autophagy in hypoxia-injured H9c2 cells, while HGF receptor inhibitor, SU11274 yielded opposite effect. What's more, NF-kappa B signaling was activated by Ad-HGF in a dose-dependent manner, and the NF-kappa B inhibitor PDTC could efficiently inhibit the activation of autophagy induced by Ad-HGF. Taken together, our findings demonstrated that Ad-HGF promoted autophagy in hypoxia-injured H9c2 cells and the protective effect of adaptable autophagy was mediated by activating NF-kappa B signaling, which suggested a new potential pathway of HGF protecting myocardium from hypoxia.

• 出版日期2016
• 单位南京医科大学