PMID- 18776126
OWN - NLM
STAT- MEDLINE
DCOM- 20090106
LR  - 20220410
IS  - 1533-3450 (Electronic)
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 19
IP  - 12
DP  - 2008 Dec
TI  - Toll-like receptor 9 affects severity of IgA nephropathy.
PG  - 2384-95
LID - 10.1681/ASN.2007121311 [doi]
AB  - Environmental pathogens are suspected to aggravate renal injury in IgA 
      nephropathy (IgAN), but neither underlying mechanisms nor specific exogenous 
      antigens have been identified. In this study, a genome-wide scan of ddY mice, 
      which spontaneously develop IgAN, was performed, and myeloid differentiation 
      factor 88 (MyD88) was identified as a candidate gene for progression of renal 
      injury (chi(2) = 21.103, P = 0.00017). For evaluation of the potential influence 
      of environmental pathogens on progression of renal injury, ddY mice were housed 
      in either conventional or specific pathogen-free conditions. Expression of genes 
      encoding toll-like receptors (TLR) and the signaling molecule MyD88 were 
      quantified by real-time reverse transcription-PCR in splenocytes. Although the 
      housing conditions did not affect the prevalence of IgAN, the severity of renal 
      injuries was higher in the conventionally housed group. Mice that had IgAN and 
      were housed in conventional conditions had higher levels of TLR9 and MyD88 
      transcripts than mice that had IgAN and were housed in specific pathogen-free 
      conditions. Furthermore, nasal challenge with CpG-oligodeoxynucleotides, which 
      are ligands for TLR9, aggravated renal injury, led to strong Th1 polarization, 
      and increased serum and mesangial IgA. For investigation of whether these results 
      may be generalizable to humans, single-nucleotide polymorphisms in the TLR9 and 
      MyD88 genes were analyzed in two cohorts of patients with IgAN; an association 
      was observed between TLR9 polymorphisms and disease progression. In summary, 
      these findings suggest that activation of the TLR9/MyD88 pathway by common 
      antigens may affect the severity of IgAN.
FAU - Suzuki, Hitoshi
AU  - Suzuki H
AD  - Division of Nephrology, Department of Internal Medicine, Juntendo University 
      School of Medicine, Tokyo, Japan.
FAU - Suzuki, Yusuke
AU  - Suzuki Y
FAU - Narita, Ichiei
AU  - Narita I
FAU - Aizawa, Masashi
AU  - Aizawa M
FAU - Kihara, Masao
AU  - Kihara M
FAU - Yamanaka, Takahiro
AU  - Yamanaka T
FAU - Kanou, Tatsuya
AU  - Kanou T
FAU - Tsukaguchi, Hiroyasu
AU  - Tsukaguchi H
FAU - Novak, Jan
AU  - Novak J
FAU - Horikoshi, Satoshi
AU  - Horikoshi S
FAU - Tomino, Yasuhiko
AU  - Tomino Y
LA  - eng
GR  - DK080301/DK/NIDDK NIH HHS/United States
GR  - DK064400/DK/NIDDK NIH HHS/United States
GR  - R01 DK078244/DK/NIDDK NIH HHS/United States
GR  - DK078244/DK/NIDDK NIH HHS/United States
GR  - R56 DK078244/DK/NIDDK NIH HHS/United States
GR  - R24 DK064400/DK/NIDDK NIH HHS/United States
GR  - R21 DK080301/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080905
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (MYD88 protein, human)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (TLR9 protein, human)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
MH  - Animals
MH  - CpG Islands
MH  - Disease Progression
MH  - Genetic Predisposition to Disease
MH  - Glomerulonephritis, IGA/*genetics/*metabolism
MH  - Humans
MH  - Japan
MH  - Mice
MH  - Models, Biological
MH  - Myeloid Differentiation Factor 88/*metabolism
MH  - Polymorphism, Genetic
MH  - Spleen/cytology/microbiology
MH  - Toll-Like Receptor 9/*metabolism
PMC - PMC2588104
EDAT- 2008/09/09 09:00
MHDA- 2009/01/07 09:00
PMCR- 2009/12/01
CRDT- 2008/09/09 09:00
PHST- 2008/09/09 09:00 [pubmed]
PHST- 2009/01/07 09:00 [medline]
PHST- 2008/09/09 09:00 [entrez]
PHST- 2009/12/01 00:00 [pmc-release]
AID - ASN.2007121311 [pii]
AID - 1311 [pii]
AID - 10.1681/ASN.2007121311 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2008 Dec;19(12):2384-95. doi: 10.1681/ASN.2007121311. Epub 2008 
      Sep 5.