AI Article Synopsis

  • Naked mole rats (NMRs) show remarkable tolerance to long-term low oxygen levels (hypoxia), and this study investigates the roles of HIF-1α and VEGFA in their adaptation to hypoxia.
  • The researchers compared primary hepatic stellate cells (HSCs) from NMRs and mice, finding higher HIF-1α and VEGFA levels in NMRs, but apoptosis rates increased when HIF-1α was inhibited or VEGFA was blocked.
  • The findings suggest that HIF-1α is crucial for hypoxia adaptation in NMRs, and its activation leads to increased VEGFA expression, highlighting a potential protective mechanism against hypoxia-induced cell death.

Article Abstract

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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746355PMC
http://dx.doi.org/10.18632/oncotarget.22767DOI Listing

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