PMID- 24446488
OWN - NLM
STAT- MEDLINE
DCOM- 20140414
LR  - 20220408
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 211
IP  - 2
DP  - 2014 Feb 10
TI  - Muller glia cells regulate Notch signaling and retinal angiogenesis via the 
      generation of 19,20-dihydroxydocosapentaenoic acid.
PG  - 281-95
LID - 10.1084/jem.20131494 [doi]
AB  - Cytochrome P450 (CYP) epoxygenases generate bioactive lipid epoxides which can be 
      further metabolized to supposedly less active diols by the soluble epoxide 
      hydrolase (sEH). As the role of epoxides and diols in angiogenesis is unclear, we 
      compared retinal vasculature development in wild-type and sEH(-/-) mice. Deletion 
      of the sEH significantly delayed angiogenesis, tip cell, and filopodia formation, 
      a phenomenon associated with activation of the Notch signaling pathway. In the 
      retina, sEH was localized in Muller glia cells, and Muller cell-specific sEH 
      deletion reproduced the sEH(-/-) retinal phenotype. Lipid profiling revealed that 
      sEH deletion decreased retinal and Muller cell levels of 
      19,20-dihydroxydocosapentaenoic acid (DHDP), a diol of docosahexenoic acid (DHA). 
      19,20-DHDP suppressed endothelial Notch signaling in vitro via inhibition of the 
      gamma-secretase and the redistribution of presenilin 1 from lipid rafts. Moreover, 
      19,20-DHDP, but not the parent epoxide, was able to rescue the defective 
      angiogenesis in sEH(-/-) mice as well as in animals lacking the Fbxw7 ubiquitin 
      ligase, which demonstrate strong basal activity of the Notch signaling cascade. 
      These studies demonstrate that retinal angiogenesis is regulated by a novel form 
      of neuroretina-vascular interaction involving the sEH-dependent generation of a 
      diol of DHA in Muller cells.
FAU - Hu, Jiong
AU  - Hu J
AD  - Institute for Vascular Signaling, Centre for Molecular Medicine, Johann Wolfgang 
      Goethe University and DZHK (German Centre for Cardiovascular Research) partner 
      site Rhine-Main, 60590 Frankfurt, Germany.
FAU - Popp, Rudiger
AU  - Popp R
FAU - Fromel, Timo
AU  - Fromel T
FAU - Ehling, Manuel
AU  - Ehling M
FAU - Awwad, Khader
AU  - Awwad K
FAU - Adams, Ralf H
AU  - Adams RH
FAU - Hammes, Hans-Peter
AU  - Hammes HP
FAU - Fleming, Ingrid
AU  - Fleming I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140120
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (F-Box Proteins)
RN  - 0 (F-Box-WD Repeat-Containing Protein 7)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Fbxw7 protein, mouse)
RN  - 0 (Receptors, Notch)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
SB  - IM
MH  - Amyloid Precursor Protein Secretases/metabolism
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Ependymoglial Cells/*metabolism
MH  - Epoxide Hydrolases/deficiency/genetics/*metabolism
MH  - F-Box Proteins/genetics/metabolism
MH  - F-Box-WD Repeat-Containing Protein 7
MH  - Fatty Acids, Unsaturated/*biosynthesis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - *Neovascularization, Physiologic
MH  - Receptors, Notch/*metabolism
MH  - Retinal Vessels/cytology/*growth & development/*metabolism
MH  - Signal Transduction
MH  - Ubiquitin-Protein Ligases/deficiency/genetics/metabolism
PMC - PMC3920554
EDAT- 2014/01/22 06:00
MHDA- 2014/04/15 06:00
PMCR- 2014/08/10
CRDT- 2014/01/22 06:00
PHST- 2014/01/22 06:00 [entrez]
PHST- 2014/01/22 06:00 [pubmed]
PHST- 2014/04/15 06:00 [medline]
PHST- 2014/08/10 00:00 [pmc-release]
AID - jem.20131494 [pii]
AID - 20131494 [pii]
AID - 10.1084/jem.20131494 [doi]
PST - ppublish
SO  - J Exp Med. 2014 Feb 10;211(2):281-95. doi: 10.1084/jem.20131494. Epub 2014 Jan 
      20.