PMID- 25968940
OWN - NLM
STAT- MEDLINE
DCOM- 20160524
LR  - 20181202
IS  - 1029-2470 (Electronic)
IS  - 1029-2470 (Linking)
VI  - 49
IP  - 9
DP  - 2015
TI  - Arctigenin suppresses transforming growth factor-beta1-induced expression of 
      monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal 
      transition through reactive oxygen species-dependent ERK/NF-kappaB signaling pathway 
      in renal tubular epithelial cells.
PG  - 1095-113
LID - 10.3109/10715762.2015.1038258 [doi]
AB  - Transforming growth factor-beta1 (TGF-beta1) induces expression of the proinflammatory 
      and profibrotic cytokine monocyte chemoattractant protein-1 (MCP-1) in tubular 
      epithelial cells (TECs) and thereby contributes to the tubular 
      epithelial-mesenchymal transition (EMT), which in turn leads to the progression 
      of tubulointerstitial inflammation into tubulointerstitial fibrosis. Exactly how 
      TGF-beta1 causes MCP-1 overexpression and subsequent EMT is not well understood. 
      Using human tubular epithelial cultures, we found that TGF-beta1 upregulated the 
      expression of reduced nicotinamide adenine dinucleotide phosphate oxidases 2 and 
      4 and their regulatory subunits, inducing the production of reactive oxygen 
      species. These reactive species activated a signaling pathway mediated by 
      extracellular signal-regulated kinase (ERK1/2) and nuclear factor-kappaB (NF-kappaB), 
      which upregulated expression of MCP-1. Incubating cultures with TGF-beta1 was 
      sufficient to induce hallmarks of EMT, such as downregulation of epithelial 
      marker proteins (E-cadherin and zonula occludens-1), induction of mesenchymal 
      marker proteins (alpha-smooth muscle actin, fibronectin, and vimentin), and elevated 
      cell migration and invasion in an EMT-like manner. Overexpressing MCP-1 in cells 
      exposed to TGF-beta1 exacerbated these EMT-like changes. Pretreating cells with the 
      antioxidant and anti-inflammatory compound arctigenin (ATG) protected them 
      against these TGF-beta1-induced EMT-like changes; the compound worked by inhibiting 
      the ROS/ERK1/2/NF-kappaB pathway to decrease MCP-1 upregulation. These findings 
      suggest ATG as a new therapeutic candidate to inhibit or even reverse tubular 
      EMT-like changes during progression to tubulointerstitial fibrosis, and they 
      provide the first clues to how ATG may work.
FAU - Li, A
AU  - Li A
AD  - Department of Pharmacology and Pharmaceutical Sciences, College of Pharmacy and 
      Bioengineering, Chongqing University of Technology , Chongqing , P. R. China.
FAU - Wang, J
AU  - Wang J
FAU - Zhu, D
AU  - Zhu D
FAU - Zhang, X
AU  - Zhang X
FAU - Pan, R
AU  - Pan R
FAU - Wang, R
AU  - Wang R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150513
PL  - England
TA  - Free Radic Res
JT  - Free radical research
JID - 9423872
RN  - 0 (Antigens, CD)
RN  - 0 (Antioxidants)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CDH1 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Furans)
RN  - 0 (Lignans)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (TJP1 protein, human)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Zonula Occludens-1 Protein)
RN  - EC 1.6.3.- (CYBB protein, human)
RN  - EC 1.6.3.- (NADPH Oxidase 2)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.- (NOX4 protein, human)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - U76MR9VS6M (arctigenin)
SB  - IM
MH  - Antigens, CD
MH  - Antioxidants/chemistry
MH  - Cadherins/metabolism
MH  - Cell Movement
MH  - Chemokine CCL2/*metabolism
MH  - Epithelial Cells/*drug effects/metabolism
MH  - *Epithelial-Mesenchymal Transition
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Fibrosis
MH  - Furans/*chemistry
MH  - Gene Expression Regulation
MH  - Humans
MH  - Inflammation/metabolism
MH  - Kidney Tubules/cytology
MH  - Lignans/*chemistry
MH  - Membrane Glycoproteins/metabolism
MH  - Microscopy, Fluorescence
MH  - NADPH Oxidase 2
MH  - NADPH Oxidase 4
MH  - NADPH Oxidases/metabolism
MH  - NF-kappa B/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - *Signal Transduction
MH  - Transforming Growth Factor beta1/*pharmacology
MH  - Zonula Occludens-1 Protein/metabolism
OTO - NOTNLM
OT  - NADPH oxidase
OT  - antioxidant capacity
OT  - hydrogen peroxide
OT  - redox signaling
OT  - redox-sensitive transcription factors
EDAT- 2015/05/15 06:00
MHDA- 2016/05/25 06:00
CRDT- 2015/05/14 06:00
PHST- 2015/05/14 06:00 [entrez]
PHST- 2015/05/15 06:00 [pubmed]
PHST- 2016/05/25 06:00 [medline]
AID - 10.3109/10715762.2015.1038258 [doi]
PST - ppublish
SO  - Free Radic Res. 2015;49(9):1095-113. doi: 10.3109/10715762.2015.1038258. Epub 
      2015 May 13.