Autophagy attenuates endothelial-to-mesenchymal transition by promoting Snail degradation in human cardiac microvascular endothelial cells
| Autor: | Zeqi Zheng, Yanqin Hao, Zhiyong Zhang, Bingong Li, Jin Zou, Fuyou Liu, Xuan Ke, Xingxing Li, Yanhua Liu, Xuelian Li |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
autophagy Epithelial-Mesenchymal Transition Angiogenesis Cardiac fibrosis ndothelial-to-mensenchymal transition Biophysics Snail Biology Biochemistry Cell Line 03 medical and health sciences biology.animal medicine Humans Autocrine signalling Molecular Biology Research Articles Tube formation hypoxia TGFβ2 Mesenchymal stem cell Autophagy Endothelial Cells Cell Biology Hypoxia (medical) medicine.disease Coronary Vessels Cell Hypoxia Cell biology 030104 developmental biology Microvessels Proteolysis Snail Family Transcription Factors medicine.symptom Research Article |
| Zdroj: | Bioscience Reports |
| ISSN: | 1573-4935 |
| Popis: | Endothelial-to-mesenchymal transition (EndMT) mainly exists in cardiovascular development and disease progression, and is well known to contribute to cardiac fibrosis. Recent studies indicated that autophagy also participates in the regulation of cardiac fibrosis. However, the precise role of autophagy in cardiac fibrosis and the underlying molecular mechanism remain unclear. The present study aimed to explore the role of autophagy in EndMT, reveal the underlying molecular mechanism, and seek new therapy for cardiac fibrosis. In the present study, we found that EndMT and autophagy were induced simultaneously by hypoxia in human cardiac microvascular endothelial cells (HCMECs). Rapamycin, an autophagy enhancer, attenuated EndMT with promoting angiogenesis, while 3-methyladenine (3-MA) and chloroquine (CQ), agents that inhibit autophagy, accelerated the progression accompanied by the decrease in counts of tube formation under hypoxia conditions. Interestingly, intervening autophagy by rapamycin, 3-MA, or CQ did not affect hypoxia-induced autocrine TGFβ signaling, but changed the expression of Snail protein without alterations in the expression of Snail mRNA. Furthermore, the colocalization of LC3 and Snail indicated that autophagy might mediate Snail degradation under hypoxia conditions in HCMECs. Interaction of p62, the substrate of autophagy, with Snail by co-immunoprecipitation especially in hypoxia-incubated cells confirmed the hypothesis. In conclusion, autophagy serves as a cytoprotective mechanism against EndMT to promote angiogenesis by degrading Snail under hypoxia conditions, suggesting that autophagy targetted therapeutic strategies may be applicable for cardiac fibrosis by EndMT. |
| Databáze: | OpenAIRE |
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