PMID- 24260304
OWN - NLM
STAT- MEDLINE
DCOM- 20140707
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 11
DP  - 2013
TI  - SUMOylation of PPARgamma by rosiglitazone prevents LPS-induced NCoR degradation 
      mediating down regulation of chemokines expression in renal proximal tubular 
      cells.
PG  - e79815
LID - 10.1371/journal.pone.0079815 [doi]
LID - e79815
AB  - Rosiglitazone (RGL), a synthetic agonist for peroxisome proliferator activated 
      receptor gamma (PPARgamma), exhibits a potent anti-inflammatory activity by attenuating 
      local infiltration of neutrophils and monocytes in the renal interstitium. To 
      evaluate the mechanisms that account for inhibiting inflammatory cells 
      infiltration, we investigated the effect of RGL on chemokines secretion and 
      nuclear factor-kappa B (NF-kappaB) activation in human renal proximal tubular cells 
      (PTCs). We demonstrated that RGL significantly inhibited lipopolysaccharide 
      (LPS)-induced interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) 
      production in a dose-dependent manner, without appreciable cytotoxicity. 
      Chromatin immunoprecipitation (ChIP) assays clearly revealed that, RGL inhibited 
      p65 binding to IL-8/MCP-1 gene promoters in LPS-stimulated PTCs. Interestingly, 
      further experiments showed RGL reversed LPS-induced nuclear receptor corepressor 
      (NCoR) degradation. In addition, knockdown of protein inhibitor of activated 
      STAT1 (PIAS1), an indispensable small ubiquitin-like modi fi er (SUMO) ligase, 
      abrogated the effects of RGL on antagonizing LPS-induced IL-8/MCP-1 
      overexpression and NCoR degradation. These findings suggest that, RGL activates 
      PPARgamma SUMOylation, inhibiting NCoR degradation and NF-kappaB activation in 
      LPS-stimulated PTCs, which in turn decrease chemokines expression. The results 
      unveil a new mechanism triggered by RGL for prevention of tubular inflammatory 
      injury.
FAU - Lu, Ying
AU  - Lu Y
AD  - Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, 
      Shanghai, China ; Department of Nephrology, Second Affiliated Hospital of Soochow 
      University, Suzhou, China.
FAU - Zhou, Qiao
AU  - Zhou Q
FAU - Shi, Yongbing
AU  - Shi Y
FAU - Liu, Jian
AU  - Liu J
FAU - Zhong, Fang
AU  - Zhong F
FAU - Hao, Xu
AU  - Hao X
FAU - Li, Cong
AU  - Li C
FAU - Chen, Nan
AU  - Chen N
FAU - Wang, Weiming
AU  - Wang W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131108
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Co-Repressor Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (PPAR gamma)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (Thiazolidinediones)
RN  - 05V02F2KDG (Rosiglitazone)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Cell Line
MH  - Chemokine CCL2/genetics/metabolism
MH  - Chemokines/genetics/*metabolism
MH  - Co-Repressor Proteins/genetics/*metabolism
MH  - Down-Regulation/*drug effects/genetics
MH  - Humans
MH  - Kidney Tubules, Proximal/drug effects/*metabolism
MH  - Ligases/genetics/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - PPAR gamma/genetics/*metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Proteolysis/drug effects
MH  - Rosiglitazone
MH  - STAT1 Transcription Factor/genetics/metabolism
MH  - Sumoylation/*drug effects/genetics
MH  - Thiazolidinediones/*pharmacology
PMC - PMC3832667
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/11/22 06:00
MHDA- 2014/07/08 06:00
PMCR- 2013/11/08
CRDT- 2013/11/22 06:00
PHST- 2013/06/21 00:00 [received]
PHST- 2013/10/04 00:00 [accepted]
PHST- 2013/11/22 06:00 [entrez]
PHST- 2013/11/22 06:00 [pubmed]
PHST- 2014/07/08 06:00 [medline]
PHST- 2013/11/08 00:00 [pmc-release]
AID - PONE-D-13-25804 [pii]
AID - 10.1371/journal.pone.0079815 [doi]
PST - epublish
SO  - PLoS One. 2013 Nov 8;8(11):e79815. doi: 10.1371/journal.pone.0079815. eCollection 
      2013.