PMID- 24063814
OWN - NLM
STAT- MEDLINE
DCOM- 20140625
LR  - 20131125
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 26
IP  - 1
DP  - 2014 Jan
TI  - Cyr61 induces the expression of monocyte chemoattractant protein-1 via the 
      integrin alphanubeta3, FAK, PI3K/Akt, and NF-kappaB pathways in retinal vascular endothelial 
      cells.
PG  - 133-40
LID - S0898-6568(13)00261-1 [pii]
LID - 10.1016/j.cellsig.2013.08.026 [doi]
AB  - Diabetes causes a number of metabolic and physiological abnormalities in the 
      retina. Many of the molecular and physiological abnormalities that develop during 
      diabetic retinopathy are due to inflammation. Monocyte chemoattractant protein-1 
      (MCP-1) is an important factor involved in diabetic retinopathy. In a previous 
      study, we found that cysteine-rich 61 (Cyr61), an important angiogenic factor, 
      also plays an important role in diabetic retinopathy. In addition to the direct 
      effects of Cyr61, we observed that Cyr61 can induce the expression of MCP-1. 
      However, the mechanism through which this occurs is not completely understood in 
      chorioretinal vascular endothelial cells. We therefore investigated the effects 
      of Cyr61 on MCP-1 expression in this cell type. Cyr61 stimulated the expression 
      of MCP-1 at the mRNA, protein, and secreted protein levels in a dose-dependent 
      and time-dependent manner. Both total MCP-1 levels and secreted MCP-1 levels were 
      attenuated during the response to Cyr61 stimulation by pretreatment with integrin 
      alphanubeta3-blocking antibodies, a FAK inhibitor (PF573228), a PI3K inhibitor 
      (LY294002), and an Akt inhibitor (A6730). Electrophoretic mobility shift assays 
      revealed that the above inhibitors suppressed the activation of NF-kappaB. 
      Additionally, deletion of the NF-kappaB-binding element in the MCP-1 gene promoter 
      led to a decrease in expression in luciferase reporter assays. These results show 
      that the induction of MCP-1 by Cyr61 is mediated through the activation of the 
      integrin alphanubeta3, FAK, PI3K/Akt, and IKK/NF-kappaB pathways in chorioretinal vascular 
      endothelial cells.
CI  - (c) 2013 Elsevier Inc. All rights reserved.
FAU - You, Jian-Jang
AU  - You JJ
AD  - Department of Ophthalmology, Keelung General Hospital, Department of Health, The 
      Executive Yuan, No. 268, Xin 2nd Road, Keelung 20147, Taiwan.
FAU - Yang, Chang-Hao
AU  - Yang CH
FAU - Yang, Chung-May
AU  - Yang CM
FAU - Chen, Muh-Shy
AU  - Chen MS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130922
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cysteine-Rich Protein 61)
RN  - 0 (Integrin alphaVbeta3)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cell Line
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Cysteine-Rich Protein 61/*metabolism
MH  - Endothelial Cells/*metabolism
MH  - Focal Adhesion Protein-Tyrosine Kinases/*metabolism
MH  - Gene Expression Regulation
MH  - Haplorhini
MH  - Integrin alphaVbeta3/*metabolism
MH  - Models, Biological
MH  - NF-kappa B/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-akt
MH  - Retinal Vessels/cytology
MH  - Signal Transduction/genetics
MH  - Transcription, Genetic
OTO - NOTNLM
OT  - Akt
OT  - Cyr61
OT  - DMEM
OT  - Dulbecco's modified Eagle's medium
OT  - EMSA
OT  - FAK
OT  - FBS
OT  - I kappa B kinase
OT  - IKK
OT  - Integrin
OT  - MCP-1
OT  - NF-kappaB
OT  - PDTC
OT  - PI3K
OT  - PKB/Akt
OT  - Signal transduction
OT  - cysteine-rich 61
OT  - electrophoretic mobility shift assays
OT  - fetal bovine serum
OT  - focal adhesion kinase
OT  - monocyte chemoattractant protein-1
OT  - nuclear factor kappa B
OT  - phosphatidylinositol-3 kinase
OT  - protein kinase B/Akt
OT  - pyrrolidine dithiocarbamate
EDAT- 2013/09/26 06:00
MHDA- 2014/06/26 06:00
CRDT- 2013/09/26 06:00
PHST- 2013/03/17 00:00 [received]
PHST- 2013/08/04 00:00 [revised]
PHST- 2013/08/27 00:00 [accepted]
PHST- 2013/09/26 06:00 [entrez]
PHST- 2013/09/26 06:00 [pubmed]
PHST- 2014/06/26 06:00 [medline]
AID - S0898-6568(13)00261-1 [pii]
AID - 10.1016/j.cellsig.2013.08.026 [doi]
PST - ppublish
SO  - Cell Signal. 2014 Jan;26(1):133-40. doi: 10.1016/j.cellsig.2013.08.026. Epub 2013 
      Sep 22.