PMID- 21115116
OWN - NLM
STAT- MEDLINE
DCOM- 20111220
LR  - 20171116
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 63
IP  - 3
DP  - 2011 Mar
TI  - Pigment epithelium-derived factor (PEDF) inhibits proximal tubular cell injury in 
      early diabetic nephropathy by suppressing advanced glycation end products 
      (AGEs)-receptor (RAGE) axis.
PG  - 241-8
LID - 10.1016/j.phrs.2010.11.008 [doi]
AB  - Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein with 
      anti-angiogenic and anti-inflammatory properties, and it could block the 
      development and progression of experimental diabetic retinopathy. However, a role 
      for PEDF in early experimental diabetic nephropathy is not fully understood. 
      Advanced glycation end products (AGEs) and their receptor (RAGE) axis stimulates 
      oxidative stress generation and subsequently evokes inflammatory and fibrogenic 
      reactions in renal tubular cells, thereby playing a role in diabetic nephropathy. 
      Therefore, this study investigated whether PEDF could prevent AGE-elicited 
      tubular cell injury in early diabetic nephropathy. Human proximal tubular cells 
      were incubated with or without AGE-bovine serum albumin in the presence or 
      absence of PEDF. Streptozotocin-induced diabetic rats were treated with or 
      without intravenous injection of PEDF for 4 weeks. Gene expression was analyzed 
      by quantitative real-time reverse transcription-polymerase chain reactions. 
      Reactive oxygen species (ROS) was measured with dihydroethidium staining. PEDF or 
      antibodies raised against RAGE inhibited the AGE-induced RAGE gene expression and 
      subsequently reduced ROS generation, monocyte chemoattractant protein-1 (MCP-1) 
      and transforming growth factor-beta (TGF-beta), fibronectin and type IV collagen mRNA 
      levels in proximal tubular cells. RAGE gene expression, ROS generation and MCP-1 
      and TGF-beta mRNA levels were significantly increased in diabetic kidney, which were 
      suppressed by administration of PEDF. Our present data suggest that PEDF could 
      play a protective role against tubular injury in diabetic nephropathy by 
      attenuating the deleterious effects of AGEs via down-regulation of RAGE 
      expression. Administration of PEDF may offer a promising strategy for halting the 
      development of diabetic nephropathy.
CI  - Copyright (c) 2010 Elsevier Ltd. All rights reserved.
FAU - Maeda, Sayaka
AU  - Maeda S
AD  - Department of Pathophysiology and Therapeutics of Diabetic Vascular 
      Complications, Kurume University School of Medicine, Kurume, Japan.
FAU - Matsui, Takanori
AU  - Matsui T
FAU - Takeuchi, Masayoshi
AU  - Takeuchi M
FAU - Yoshida, Yumiko
AU  - Yoshida Y
FAU - Yamakawa, Ryoji
AU  - Yamakawa R
FAU - Fukami, Kei
AU  - Fukami K
FAU - Yamagishi, Sho-ichi
AU  - Yamagishi S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101127
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Eye Proteins)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Serpins)
RN  - 0 (pigment epithelium-derived factor)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cells, Cultured
MH  - Diabetic Nephropathies/*metabolism/pathology/*prevention & control
MH  - Eye Proteins/*therapeutic use
MH  - Glycation End Products, Advanced/antagonists & inhibitors/physiology
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Kidney Tubules, Proximal/*drug effects/*metabolism/pathology
MH  - Male
MH  - Nerve Growth Factors/*therapeutic use
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/*antagonists & inhibitors/*biosynthesis
MH  - Serpins/*therapeutic use
EDAT- 2010/12/01 06:00
MHDA- 2011/12/21 06:00
CRDT- 2010/12/01 06:00
PHST- 2010/08/15 00:00 [received]
PHST- 2010/11/21 00:00 [revised]
PHST- 2010/11/22 00:00 [accepted]
PHST- 2010/12/01 06:00 [entrez]
PHST- 2010/12/01 06:00 [pubmed]
PHST- 2011/12/21 06:00 [medline]
AID - S1043-6618(10)00221-5 [pii]
AID - 10.1016/j.phrs.2010.11.008 [doi]
PST - ppublish
SO  - Pharmacol Res. 2011 Mar;63(3):241-8. doi: 10.1016/j.phrs.2010.11.008. Epub 2010 
      Nov 27.