HIF-1α contributes to hypoxia adaptation of the naked mole rat
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Bang Xiao1,*, Shiyong Wang2,*, Guoshi Yang2,*, Xiaoxi Sun2,*, Shanmin Zhao1, Lifang Lin1, Jishuai Cheng1, Wenjing Yang1, Wei Cong1, Wei Sun1, Guanghan Kan3 and Shufang Cui1
1Laboratory Animal Centre, The Second Military Medical University, Shanghai 200433, China
2Division of Teaching Support, Training Department, The Second Military Medical University, Shanghai 200433, China
3China Astronaut Research and Training Center, Beijing 100094, China
*These authors contributed equally to this work
Shufang Cui, email: email@example.com
Guanghan Kan, email: firstname.lastname@example.org
Keywords: HIF-1α; VEGFA; naked mole rat; hypoxic adaptation
Received: July 22, 2017 Accepted: November 11, 2017 Published: November 30, 2017
Background/Aims: Naked mole rats (NMRs) spend their lives in burrow systems containing very low levels of oxygen, indicating long-term hypoxic exposure, and suggesting that pathological changes caused by hypoxia are attenuated or absent in this hypoxia-tolerant species. The mechanisms underlying NMRs hypoxia tolerance remain poorly understood. In this study, we explored whether hypoxia inducible factor 1α (HIF-1α), and vascular endothelial growth factor A (VEGFA) play a role in NMRs adaption to hypoxia.
Methods: Primary hepatic stellate cells (HSCs) isolated from NMRs and mice were treated with 50 μM YC-1, 50 μM KC7F2 or VEGFA siRNA. HIF-1α or VEGFA expression was detected by Western blot and real-time PCR. Apoptosis was determined by flow cytometry. The expression of autophagy markers (LC3 and p62) was detected by Western blot.
Results: Our results showed that HIF-1α and VEGFA expression in NMRs was significantly higher than in hypoxia-sensitive mice. Inhibition of HIF-1α expression induced apoptosis in both NMR and mouse HSCs following hypoxia. However, blocking VEGFA transcription results in a significant increase of apoptosis in both NMR and mouse HSCs before and after hypoxia. In addition, NMR HSCs displayed higher levels of autophagy (ratio of LC3ΙΙ/LC3Ι = 9.6) than mouse HSCs (relative ratio of LC3ΙΙ/ LC3Ι = 4.9) under hypoxic conditions.
Conclusion: We conclude that HIF-1α activation may be an important mechanism for hypoxia adaption. However, high expression of VEGFA follows HIF-1α activation in NMRs.
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