PMID- 27659793
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Sep 23
TI  - Downregulation of angiotensin type 1 receptor and nuclear factor-kappaB by sirtuin 1 
      contributes to renoprotection in unilateral ureteral obstruction.
PG  - 33705
LID - 10.1038/srep33705 [doi]
LID - 33705
AB  - Activation of sirtuin 1 (Sirt1) attenuates unilateral ureteral obstruction 
      (UUO)-induced inflammation and fibrosis, suggesting that Sirt1 may prevent 
      tubulointerstitial fibrosis. In this study, we explored changes in the expression 
      of Sirt1 in the kidneys of UUO-treated rats and evaluated the effects of Sirt1 
      activation or inhibition on renal pathology and mediators of UUO pathogenesis, 
      especially angiotensin II and nuclear factor (NF)-kappaB, in rats and rat renal 
      fibroblasts. Sirt1 expression increased in the obstructed kidney but not in the 
      contralateral kidney and was mainly detected in tubulointerstitial cells. 
      Resveratrol, a Sirt1 activator, decreased UUO-induced inflammation and fibrosis, 
      while sirtinol, a Sirt1 inhibitor, enhanced UUO-induced inflammation. UUO 
      increased renal angiotensin type 1 receptor (AT1R), NF-kappaB, monocyte chemotactic 
      protein 1 (MCP-1), and fibronectin expression. Resveratrol attenuated these 
      UUO-induced changes, whereas sirtinol enhanced them, with the exception of 
      fibronectin. In renal fibroblasts, Sirt1 overexpression reduced AT1R and NF-kappaB 
      levels, while Sirt1 knockdown had the opposite effects. Sirtinol increased the 
      levels of AT1R, NF-kappaB, MCP-1, and connective tissue growth factor (CTGF), while 
      resveratrol reduced AT1R levels. Our results suggested that Sirt1 inhibited AT1R 
      and NF-kappaB expression in renal fibroblasts and that these mechanisms may play 
      roles in alleviating UUO-induced damages.
FAU - Yang, Shao-Yu
AU  - Yang SY
AD  - Graduate Institute of Clinical Medicine, National Taiwan University College of 
      Medicine, Taipei, Taiwan.
AD  - Department of Internal Medicine, National Taiwan University Hospital and College 
      of Medicine, Taipei, Taiwan.
FAU - Lin, Shuei-Liong
AU  - Lin SL
AD  - Department of Internal Medicine, National Taiwan University Hospital and College 
      of Medicine, Taipei, Taiwan.
AD  - Graduate Institute of Physiology, National Taiwan University College of Medicine, 
      Taipei, Taiwan.
FAU - Chen, Yung-Ming
AU  - Chen YM
AD  - Department of Internal Medicine, National Taiwan University Hospital and College 
      of Medicine, Taipei, Taiwan.
AD  - Department of Internal Medicine, National Taiwan University Hospital Yun-Lin 
      Branch, Douliou City, Taiwan.
FAU - Wu, Vin-Cent
AU  - Wu VC
AD  - Department of Internal Medicine, National Taiwan University Hospital and College 
      of Medicine, Taipei, Taiwan.
FAU - Yang, Wei-Shiung
AU  - Yang WS
AD  - Graduate Institute of Clinical Medicine, National Taiwan University College of 
      Medicine, Taipei, Taiwan.
AD  - Department of Internal Medicine, National Taiwan University Hospital and College 
      of Medicine, Taipei, Taiwan.
FAU - Wu, Kwan-Dun
AU  - Wu KD
AD  - Department of Internal Medicine, National Taiwan University Hospital and College 
      of Medicine, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20160923
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
PMC - PMC5034227
COIS- The authors declare no competing financial interests.
EDAT- 2016/09/24 06:00
MHDA- 2016/09/24 06:01
PMCR- 2016/09/23
CRDT- 2016/09/24 06:00
PHST- 2016/01/19 00:00 [received]
PHST- 2016/09/01 00:00 [accepted]
PHST- 2016/09/24 06:00 [pubmed]
PHST- 2016/09/24 06:01 [medline]
PHST- 2016/09/24 06:00 [entrez]
PHST- 2016/09/23 00:00 [pmc-release]
AID - srep33705 [pii]
AID - 10.1038/srep33705 [doi]
PST - epublish
SO  - Sci Rep. 2016 Sep 23;6:33705. doi: 10.1038/srep33705.