title: Hypoxia-induced autophagy in endothelial cells: a double-edged sword in the progression of infantile haemangioma?
abstract: OBJECTIVE
  The aim of this study was to investigate the precise role of hypoxia-induced autophagy in endothelial cells, and whether it contributes to the distinctive progression of infantile haemangioma (IH).
  
  
  RESULTS
  The endothelial cells (EOMA and HUVECs) were cultured under hypoxic conditions for indicated times (0-72 h). The results showed that short exposure of the endothelial cells to hypoxia resulted in increased cell survival and proliferation, accompanied by occurrence of autophagy. Prolonged hypoxia-induced autophagy, correlating with increased cell death, was also detected afterwards. Correspondingly, autophagy inhibition prevented the enhanced cell survival and proliferation capacity, advanced the occurrence of cell-death in early hypoxic stage, and meanwhile attenuated the ability of prolonged hypoxia in cell-death induction. Moreover, our data demonstrated that the functional transformation of hypoxia-induced autophagy, pro-survival to pro-death, was rigorously regulated by the switch between hypoxia-inducible factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR) pathways. Importantly, we also revealed the activation levels of HIF-1α and mTOR, as well as the autophagy status during the progression of IH.
  
  
  CONCLUSIONS
  This study unmasks the functional switch between HIF-1α and mTOR in regulating hypoxia-induced autophagy in endothelial cells and, more importantly, indicates its potential role in the progression of IH.
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan 430071, China.
authors: Gang
authors: G
authors: Chen
authors: Wei
authors: W
authors: Zhang
authors: Yin-Ping
authors: YP
authors: Li
authors: Jian-Gang
authors: JG
authors: Ren
authors: Ning
authors: N
authors: Xu
authors: Hui
authors: H
authors: Liu
authors: Feng-Qin
authors: FQ
authors: Wang
authors: Zhi-Jun
authors: ZJ
authors: Sun
authors: Jun
authors: J
authors: Jia
authors: Yi-Fang
authors: YF
authors: Zhao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; D016022:Case-Control Studies; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D006391:Hemangioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: C502778:ATG5 protein, human; D051017:Apoptosis Regulatory Proteins; D000071187:Autophagy-Related Protein 5; C491997:BECN1 protein, human; C090121:BNIP3 protein, human; D000071186:Beclin-1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
keywords: Autophagy; HIF-1α; Hypoxia; Infantile haemangioma; mTOR