PMID- 21113175
OWN - NLM
STAT- MEDLINE
DCOM- 20110415
LR  - 20211020
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 31
IP  - 12
DP  - 2010 Dec
TI  - Activation of Toll-like receptor 9 attenuates unilateral ureteral 
      obstruction-induced renal fibrosis.
PG  - 1583-92
LID - 10.1038/aps.2010.202 [doi]
AB  - AIM: to study whether activation of TLR9 by CpG-ODN would protect against and/or 
      reverse renal fibrosis. METHODS: animals were treated with CpG-ODN before or 
      after undergoing a unilateral ureteral obstruction (UUO) procedure. The 
      interstitial fibrotic lesions of obstructed kidneys were evaluated using 
      histology and immunohistostaining. The Th2-type cytokine profile and the 
      expression and activity of sma and mad related protein (Smad)3, signal 
      transducers and activators of transcription (Stat)3, extracellular regulated 
      protein kinases (ERK), and p38 kinase were determined using RT-PCR or Western 
      blot. RESULTS: the obstructed kidneys displayed a significant increase in 
      interstitial fibrosis, an infiltration of macrophages in the interstitium, and an 
      enhanced expression of Th2 cytokines. Prophylactic application of CpG-ODN (40 
      microg/kg every 3 days from 2 h before UUO until the 14th day after UUO) 
      suppressed the expression of alpha-smooth muscle actin, collagen deposition, and 
      hydroxyproline in the UUO kidneys of rats. Moreover, CpG-ODN not only decreased 
      the infiltration of macrophages but also inhibited the expression of chemokines 
      CCL2 and CCL5, the Th2 cytokine IL-13, and the profibrogenic cytokines 
      transforming growth factor (TGF)-beta1 and plasminogen activator inhibitor (PAI)-1 
      in UUO kidneys of rats. Importantly, therapeutic administration of CpG-ODN (10 
      microg/mouse, ip, every 3 days from the 4th day to 21st day after UUO) reversed 
      the established renal fibrosis, which was accompanied by significant reductions 
      in the activity of ERK, Smad3, and Stat3 and an increase in the activity of p38 
      kinase. CONCLUSION: the activation of TLR9 by CpG-ODN attenuates UUO-induced 
      renal fibrosis by reversing an immunosuppressive microenvironment in the fibrotic 
      renal tissue, which might be a novel therapeutic strategy against fibrotic renal 
      diseases.
FAU - XIN, Bing-mu
AU  - XIN BM
AD  - Molecular Immunology and Pharmacology Laboratory, Institute of Materia Medica, 
      Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 
      100050, China.
FAU - WANG, Xiao-xing
AU  - WANG XX
FAU - JIN, Wen
AU  - JIN W
FAU - YAN, Hui-min
AU  - YAN HM
FAU - CUI, Bing
AU  - CUI B
FAU - ZHANG, Xiao-wei
AU  - ZHANG XW
FAU - HUA, Fang
AU  - HUA F
FAU - YANG, Hong-zhen
AU  - YANG HZ
FAU - HU, Zhuo-wei
AU  - HU ZW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101129
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Actins)
RN  - 0 (CPG-oligonucleotide)
RN  - 0 (Interleukin-13)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Toll-Like Receptor 9)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Collagen/metabolism
MH  - Fibrosis
MH  - Interleukin-13/metabolism
MH  - Kidney/metabolism/*pathology
MH  - Kidney Tubules/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oligodeoxyribonucleotides/*therapeutic use
MH  - Plasminogen Activator Inhibitor 1/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Toll-Like Receptor 9/*agonists
MH  - Transforming Growth Factor beta1/metabolism
MH  - Ureteral Obstruction/metabolism/*pathology
PMC - PMC4002953
EDAT- 2010/11/30 06:00
MHDA- 2011/04/19 06:00
PMCR- 2010/12/01
CRDT- 2010/11/30 06:00
PHST- 2010/11/30 06:00 [entrez]
PHST- 2010/11/30 06:00 [pubmed]
PHST- 2011/04/19 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - aps2010202 [pii]
AID - 10.1038/aps.2010.202 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2010 Dec;31(12):1583-92. doi: 10.1038/aps.2010.202. Epub 2010 
      Nov 29.