PMID- 23533599
OWN - NLM
STAT- MEDLINE
DCOM- 20130911
LR  - 20240426
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 3
DP  - 2013
TI  - The nexus between VEGF and NFkappaB orchestrates a hypoxia-independent 
      neovasculogenesis.
PG  - e59021
LID - 10.1371/journal.pone.0059021 [doi]
LID - e59021
AB  - Nuclear Factor-Kappa B [NFkappaB] activation triggers the elevation of various 
      pro-angiogenic factors that contribute to the development and progression of 
      diabetic vasculopathies. It has been demonstrated that vascular endothelial 
      growth factor [VEGF] activates NFkappaB signaling pathway. Under the ischemic 
      microenvironments, hypoxia-inducible factor-1 [HIF-1] upregulates the expression 
      of several proangiogenic mediators, which play crucial roles in ocular 
      pathologies. Whereas YC-1, a soluble guanylyl cyclase [sGC] agonist, inhibits 
      HIF-1 and NFkappaB signaling pathways in various cell and animal models. Throughout 
      this investigation, we examined the molecular link between VEGF and NFkappaB under a 
      hypoxia-independent microenvironment in human retinal microvascular endothelial 
      cells [hRMVECs]. Our data indicate that VEGF promoted retinal neovasculogenesis 
      via NFkappaB activation, enhancement of its DNA-binding activity, and upregulating 
      NFkappaB/p65, SDF-1, CXCR4, FAK, alphaVbeta3, alpha5beta1, EPO, ET-1, and MMP-9 expression. 
      Conversely, YC-1 impaired the activation of NFkappaB and its downstream signaling 
      pathways, via attenuating IkappaB kinase phosphorylation, degradation and activation, 
      and thus suppressing p65 phosphorylation, nuclear translocation, and inhibiting 
      NFkappaB-DNA binding activity. We report for the first time that the nexus between 
      VEGF and NFkappaB is implicated in coordinating a scheme that upregulates several 
      pro-angiogenic molecules, which promotes retinal neovasculogenesis. Our data may 
      suggest the potential use of YC-1 to attenuate the deleterious effects that are 
      associated with hypoxia/ischemia-independent retinal vasculopathies.
FAU - DeNiro, Michael
AU  - DeNiro M
AD  - Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. 
      mdeniro@kkesh.med.sa
FAU - Al-Mohanna, Falah H
AU  - Al-Mohanna FH
FAU - Alsmadi, Osama
AU  - Alsmadi O
FAU - Al-Mohanna, Futwan A
AU  - Al-Mohanna FA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20130322
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Enzyme Activators)
RN  - 0 (Indazoles)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 154453-18-6 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole)
SB  - IM
RIN - PLoS One. 2019 Dec 30;14(12):e0227432. PMID: 31887132
MH  - Blotting, Western
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Enzyme Activators/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Immunohistochemistry
MH  - Indazoles/*pharmacology
MH  - Neovascularization, Physiologic/drug effects/genetics
MH  - Phosphorylation/drug effects
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription Factor RelA/*metabolism
MH  - Vascular Endothelial Growth Factor A/*pharmacology
PMC - PMC3606454
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/03/28 06:00
MHDA- 2013/09/12 06:00
PMCR- 2013/03/22
CRDT- 2013/03/28 06:00
PHST- 2013/01/09 00:00 [received]
PHST- 2013/02/09 00:00 [accepted]
PHST- 2013/03/28 06:00 [entrez]
PHST- 2013/03/28 06:00 [pubmed]
PHST- 2013/09/12 06:00 [medline]
PHST- 2013/03/22 00:00 [pmc-release]
AID - PONE-D-13-01727 [pii]
AID - 10.1371/journal.pone.0059021 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(3):e59021. doi: 10.1371/journal.pone.0059021. Epub 2013 Mar 22.