PMID- 20381502
OWN - NLM
STAT- MEDLINE
DCOM- 20101116
LR  - 20171116
IS  - 1095-9319 (Electronic)
IS  - 0026-2862 (Linking)
VI  - 80
IP  - 2
DP  - 2010 Sep
TI  - Pigment epithelium-derived factor inhibits advanced glycation end 
      product-elicited mesangial cell damage by blocking NF-kappaB activation.
PG  - 227-32
LID - 10.1016/j.mvr.2010.03.015 [doi]
AB  - Advanced glycation end products (AGE), senescent macroprotein derivatives formed 
      at an accelerated rate under hyperglycemic conditions, elicit oxidative stress 
      generation and inflammatory reactions, thus being involved in the development and 
      progression of diabetic nephropathy. Recently, we, along with others, have found 
      that pigment epithelium-derived factor (PEDF), a glycoprotein with potent 
      neuronal differentiating activity, inhibits AGE-elicited endothelial cell damage 
      through its anti-oxidative properties and blocks the progression of experimental 
      diabetic retinopathy. However, a role of PEDF in diabetic nephropathy is not 
      fully understood. In this study, we investigated whether and how PEDF could 
      protect against AGE-elicited mesangial cell damage in vitro. PEDF mRNA and 
      protein levels were decreased by the treatments of AGE. PEDF or neutralizing 
      antibody raised against RAGE (receptor for AGE) was found to inhibit the 
      AGE-induced oxidative stress generation and subsequent NF-kappaB activation in 
      mesangial cells. Further, AGE increased mRNA levels of monocyte chemoattractant 
      protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1) and plasminogen 
      activator inhibitor-1 (PAI-1) in mesangial cells, all of which were prevented by 
      the treatments with PEDF, RAGE antibody or pyrrolidine dithiocarbamate, a 
      NF-kappaB inhibitor. The present results demonstrated for the first time that 
      PEDF blocked the AGE-RAGE-mediated mesangial cell injury by inhibiting NF-kappaB 
      activation via suppression of reactive oxygen species generation. Our present 
      study suggests that substitution of PEDF proteins may be a promising strategy for 
      the treatment of diabetic nephropathy.
CI  - Copyright 2010 Elsevier Inc. All rights reserved.
FAU - Ide, Yuichiro
AU  - Ide Y
AD  - Department of Pathophysiology and Therapeutics of Diabetic Vascular 
      Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 
      830-0011, Japan.
FAU - Matsui, Takanori
AU  - Matsui T
FAU - Ishibashi, Yuji
AU  - Ishibashi Y
FAU - Takeuchi, Masayoshi
AU  - Takeuchi M
FAU - Yamagishi, Sho-ichi
AU  - Yamagishi S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100408
PL  - United States
TA  - Microvasc Res
JT  - Microvascular research
JID - 0165035
RN  - 0 (Antibodies, Blocking)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Eye Proteins)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (NFKB1 protein, human)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Pyrrolidines)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (SERPINE1 protein, human)
RN  - 0 (Serpins)
RN  - 0 (Thiocarbamates)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 0 (pigment epithelium-derived factor)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
RN  - 27432CM55Q (Serum Albumin, Bovine)
SB  - IM
MH  - Animals
MH  - Antibodies, Blocking/pharmacology
MH  - Blotting, Western
MH  - Cattle
MH  - Cell Count
MH  - Chemokine CCL2/genetics/metabolism
MH  - Diabetic Nephropathies/metabolism/physiopathology
MH  - Drug Antagonism
MH  - Eye Proteins/genetics/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Glycation End Products, Advanced/*antagonists & inhibitors/pharmacology
MH  - Humans
MH  - Mesangial Cells/*drug effects/metabolism/pathology
MH  - NF-kappa B p50 Subunit/antagonists & inhibitors/*biosynthesis
MH  - Nerve Growth Factors/genetics/*pharmacology
MH  - Oxidative Stress/drug effects
MH  - Plasminogen Activator Inhibitor 1/genetics/metabolism
MH  - Pyrrolidines/pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/immunology
MH  - Serpins/genetics/*pharmacology
MH  - Serum Albumin, Bovine/pharmacology
MH  - Thiocarbamates/pharmacology
MH  - Vascular Cell Adhesion Molecule-1/genetics/metabolism
EDAT- 2010/04/13 06:00
MHDA- 2010/11/17 06:00
CRDT- 2010/04/13 06:00
PHST- 2009/11/20 00:00 [received]
PHST- 2010/03/17 00:00 [revised]
PHST- 2010/03/30 00:00 [accepted]
PHST- 2010/04/13 06:00 [entrez]
PHST- 2010/04/13 06:00 [pubmed]
PHST- 2010/11/17 06:00 [medline]
AID - S0026-2862(10)00080-4 [pii]
AID - 10.1016/j.mvr.2010.03.015 [doi]
PST - ppublish
SO  - Microvasc Res. 2010 Sep;80(2):227-32. doi: 10.1016/j.mvr.2010.03.015. Epub 2010 
      Apr 8.