PMID- 27259982
OWN - NLM
STAT- MEDLINE
DCOM- 20190128
LR  - 20190128
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1862
IP  - 9
DP  - 2016 Sep
TI  - Regulation of angiogenin expression and epithelial-mesenchymal transition by 
      HIF-1alpha signaling in hypoxic retinal pigment epithelial cells.
PG  - 1594-607
LID - S0925-4439(16)30140-5 [pii]
LID - 10.1016/j.bbadis.2016.05.023 [doi]
AB  - Choroidal neovascularization (CNV) is a major cause of vision loss in many 
      retinal diseases. Hypoxia is determined to be a key inducer of CNV and 
      hypoxia-inducible factor-1 (HIF-1) is an important transcription factor. 
      Epithelial-mesenchymal transition (EMT) and the synthesis of proangiogenic 
      cytokines make great contributions to the development of CNV. In the present 
      study, the role of HIF-1alpha signaling in the regulation of angiogenin (ANG) 
      expression and EMT in hypoxic retinal pigment epithelial cells was investigated. 
      A significant elevation expression of ANG expression level in a mouse model of 
      laser-induced CNV was demonstrated. In a hypoxic model of ARPE-19, an increased 
      expression level of ANG and induction of EMT accompanied with stabilization and 
      nucleus translocation of HIF-1alpha. Blockage of HIF-1alpha signaling resulted in 
      inhibition of high expression of ANG and EMT features. The direct interaction 
      between HIF-1alpha and ANG promoter region was identified by ChIP-qPCR. The 
      association of RNase 4 mRNA level with HIF-1alpha signaling was also clarified in 
      APRE-19. Moreover, the exogenous ANG translocated into the nucleus, enhanced 45S 
      rRNA transcription, promoted cell proliferation and tube formation in human 
      retinal microvascular endothelial cells. In conclusion, the hypoxic conditions 
      regulate the expression of ANG and EMT via an activation of HIF-1alpha signaling. It 
      provides molecular evidence for potential therapy strategies of treating CNV.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Lai, Kairan
AU  - Lai K
AD  - Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang 
      University, Hangzhou, China; Zhejiang Provincial Key Laboratory of Ophthalmology, 
      Hangzhou, China.
FAU - Luo, Chenqi
AU  - Luo C
AD  - Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang 
      University, Hangzhou, China; Zhejiang Provincial Key Laboratory of Ophthalmology, 
      Hangzhou, China.
FAU - Zhang, Xiaobo
AU  - Zhang X
AD  - Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang 
      University, Hangzhou, China.
FAU - Ye, Panpan
AU  - Ye P
AD  - Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang 
      University, Hangzhou, China.
FAU - Zhang, Yidong
AU  - Zhang Y
AD  - Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang 
      University, Hangzhou, China.
FAU - He, Jiliang
AU  - He J
AD  - Institutes of Environmental Medicine, School of Medicine, Zhejiang University, 
      Hangzhou, China.
FAU - Yao, Ke
AU  - Yao K
AD  - Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang 
      University, Hangzhou, China; Zhejiang Provincial Key Laboratory of Ophthalmology, 
      Hangzhou, China. Electronic address: xlren@zju.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160531
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - EC 3.1.27.- (angiogenin)
RN  - EC 3.1.27.5 (Ribonuclease, Pancreatic)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia/physiology
MH  - Cell Line
MH  - Choroidal Neovascularization/etiology/metabolism/pathology
MH  - Disease Models, Animal
MH  - Epithelial-Mesenchymal Transition/*physiology
MH  - Gene Expression Regulation
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Models, Biological
MH  - Retinal Pigment Epithelium/*metabolism/*pathology
MH  - Ribonuclease, Pancreatic/*genetics
MH  - Signal Transduction
MH  - Up-Regulation
OTO - NOTNLM
OT  - Angiogenin
OT  - Choroidal neovascularization
OT  - Epithelial-mesenchymal transition
OT  - Hypoxia-inducible factor-1
OT  - RNase 4
EDAT- 2016/06/05 06:00
MHDA- 2019/01/29 06:00
CRDT- 2016/06/05 06:00
PHST- 2016/01/21 00:00 [received]
PHST- 2016/05/05 00:00 [revised]
PHST- 2016/05/27 00:00 [accepted]
PHST- 2016/06/05 06:00 [entrez]
PHST- 2016/06/05 06:00 [pubmed]
PHST- 2019/01/29 06:00 [medline]
AID - S0925-4439(16)30140-5 [pii]
AID - 10.1016/j.bbadis.2016.05.023 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2016 Sep;1862(9):1594-607. doi: 
      10.1016/j.bbadis.2016.05.023. Epub 2016 May 31.