PMID- 26932402
OWN - NLM
STAT- MEDLINE
DCOM- 20170117
LR  - 20181113
IS  - 2005-6648 (Electronic)
IS  - 1226-3303 (Print)
IS  - 1226-3303 (Linking)
VI  - 31
IP  - 2
DP  - 2016 Mar
TI  - Concomitant inhibition of renin angiotensin system and Toll-like receptor 2 
      attenuates renal injury in unilateral ureteral obstructed mice.
PG  - 323-34
LID - 10.3904/kjim.2015.004 [doi]
AB  - BACKGROUND/AIMS: There has been controversy about the role of Toll-like receptor 
      2 (TLR2) in renal injury following ureteric obstruction. Although inhibition of 
      the renin angiotensin system (RAS) reduces TLR2 expression in mice, the exact 
      relationship between TLR2 and RAS is not known. The aim of this study was to 
      determine whether the RAS modulates TLR2. METHODS: We used 8-week-old male wild 
      type (WT) and TLR2-knockout (KO) mice on a C57Bl/6 background. Unilateral 
      ureteral obstruction (UUO) was induced by complete ligation of the left ureter. 
      Angiotensin (Ang) II (1,000 ng/kg/min) and the direct renin inhibitor aliskiren 
      (25 mg/kg/day) were administrated to mice using an osmotic minipump. Molecular 
      and histologic evaluations were performed. RESULTS: Ang II infusion increased 
      mRNA expression of TLR2 in WT mouse kidneys (p < 0.05). The expression of renin 
      mRNA in TLR2-KO UUO kidneys was significantly higher than that in WT UUO kidneys 
      (p < 0.05). There were no differences in tissue injury score or mRNA expression 
      of monocyte chemotactic protein 1 (MCP-1), osteopontin (OPN), or transforming 
      growth factor beta (TGF-beta) between TLR2-KO UUO and WT UUO kidneys. However, 
      aliskiren decreased the tissue injury score and mRNA expression of TLR2, MCP-1, 
      OPN, and TGF-beta in WT UUO kidneys (p < 0.05). Aliskiren-treated TLR2-KO UUO 
      kidneys showed less kidney injury than aliskiren-treated WT UUO kidneys. 
      CONCLUSIONS: TLR2 deletion induced activation of the RAS in UUO kidneys. 
      Moreover, inhibition of both RAS and TLR2 had an additive ameliorative effect on 
      UUO injury of the kidney.
FAU - Chung, Sarah
AU  - Chung S
AD  - Department of Internal Medicine, Chungnam National University School of Medicine, 
      Daejeon, Korea.
FAU - Jeong, Jin Young
AU  - Jeong JY
AD  - Department of Internal Medicine, Chungnam National University School of Medicine, 
      Daejeon, Korea.
FAU - Chang, Yoon Kyung
AU  - Chang YK
AD  - Department of Internal Medicine, College of Medicine, Daejeon St. Mary's 
      Hospital, The Catholic University of Korea, Daejeon, Korea.
FAU - Choi, Dae Eun
AU  - Choi DE
AD  - Department of Internal Medicine, Chungnam National University School of Medicine, 
      Daejeon, Korea.
FAU - Na, Ki Ryang
AU  - Na KR
AD  - Department of Internal Medicine, Chungnam National University School of Medicine, 
      Daejeon, Korea.
FAU - Lim, Beom Jin
AU  - Lim BJ
AD  - Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
FAU - Lee, Kang Wook
AU  - Lee KW
AD  - Department of Internal Medicine, Chungnam National University School of Medicine, 
      Daejeon, Korea.
LA  - eng
PT  - Journal Article
DEP - 20160226
PL  - Korea (South)
TA  - Korean J Intern Med
JT  - The Korean journal of internal medicine
JID - 8712418
RN  - 0 (Amides)
RN  - 0 (Fumarates)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 11128-99-7 (Angiotensin II)
RN  - 502FWN4Q32 (aliskiren)
RN  - EC 3.4.23.15 (Renin)
SB  - IM
MH  - Amides/*pharmacology
MH  - Angiotensin II/pharmacology
MH  - Animals
MH  - Disease Models, Animal
MH  - Fibrosis
MH  - Fumarates/*pharmacology
MH  - Kidney/*drug effects/metabolism/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nephritis, Interstitial/genetics/metabolism/pathology/*prevention & control
MH  - RNA, Messenger/genetics/metabolism
MH  - Renin/*antagonists & inhibitors/metabolism
MH  - Renin-Angiotensin System/*drug effects
MH  - Toll-Like Receptor 2/deficiency/drug effects/genetics/*metabolism
MH  - Ureteral Obstruction/*drug therapy/genetics/metabolism/pathology
PMC - PMC4773720
OTO - NOTNLM
OT  - Renin-angiotensin system
OT  - Toll-like receptor 2
OT  - Unilateral ureteral obstruction
COIS- No potential conflict of interest relevant to this article was reported.
EDAT- 2016/03/05 06:00
MHDA- 2017/01/18 06:00
PMCR- 2016/03/01
CRDT- 2016/03/03 06:00
PHST- 2015/01/06 00:00 [received]
PHST- 2015/03/20 00:00 [revised]
PHST- 2015/06/02 00:00 [accepted]
PHST- 2016/03/03 06:00 [entrez]
PHST- 2016/03/05 06:00 [pubmed]
PHST- 2017/01/18 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - kjim-2015-004 [pii]
AID - 10.3904/kjim.2015.004 [doi]
PST - ppublish
SO  - Korean J Intern Med. 2016 Mar;31(2):323-34. doi: 10.3904/kjim.2015.004. Epub 2016 
      Feb 26.