PMID- 21270242
OWN - NLM
STAT- MEDLINE
DCOM- 20110422
LR  - 20220722
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 60
IP  - 3
DP  - 2011 Mar
TI  - Activation of peroxisome proliferator-activated receptor delta inhibits 
      streptozotocin-induced diabetic nephropathy through anti-inflammatory mechanisms 
      in mice.
PG  - 960-8
LID - 10.2337/db10-1361 [doi]
AB  - OBJECTIVE: Activation of the nuclear hormone receptor peroxisome 
      proliferator-activated receptor (PPAR)-delta has been shown to improve insulin 
      resistance, adiposity, and plasma HDL levels. Several studies have reported that 
      activation of PPARdelta is atheroprotective; however, the role of PPARdelta in renal 
      function remains unclear. Here, we report the renoprotective effects of PPARdelta 
      activation in a model of streptozotocin-induced diabetic nephropathy. RESEARCH 
      DESIGN AND METHODS: Eight-week-old male C57BL/6 mice were divided into three 
      groups: 1) nondiabetic control mice, 2) diabetic mice, and 3) diabetic mice 
      treated with the PPARdelta agonist GW0742 (1 mg/kg/day). GW0742 was administered by 
      gavage for 8 weeks after inducing diabetes. RESULTS: GW0742 decreased urinary 
      albumin excretion without altering blood glucose levels. Macrophage infiltration, 
      mesangial matrix accumulation, and type IV collagen deposition were substantially 
      attenuated by GW0742. The gene expression of inflammatory mediators in the kidney 
      cortex, such as monocyte chemoattractant protein-1 (MCP-1) and osteopontin (OPN), 
      was also suppressed. In vitro studies demonstrated that PPARdelta activation 
      increased the expression of anti-inflammatory corepressor B-cell lymphoma-6, 
      which subsequently suppressed MCP-1 and OPN expression. CONCLUSIONS: These 
      findings uncover a previously unrecognized mechanism for the renoprotective 
      effects of PPARdelta agonists and support the concept that PPARdelta agonists may offer a 
      novel therapeutic approach for the treatment of diabetic nephropathy.
FAU - Matsushita, Yuichi
AU  - Matsushita Y
AD  - Department of Medicine and Clinical Science, Okayama University Graduate School 
      of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
FAU - Ogawa, Daisuke
AU  - Ogawa D
FAU - Wada, Jun
AU  - Wada J
FAU - Yamamoto, Noriko
AU  - Yamamoto N
FAU - Shikata, Kenichi
AU  - Shikata K
FAU - Sato, Chikage
AU  - Sato C
FAU - Tachibana, Hiromi
AU  - Tachibana H
FAU - Toyota, Noriko
AU  - Toyota N
FAU - Makino, Hirofumi
AU  - Makino H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110126
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Chemokine CCL2)
RN  - 0 (PPAR delta)
RN  - 0 (Proto-Oncogene Proteins c-bcl-6)
RN  - 0 (Thiazoles)
RN  - 106441-73-0 (Osteopontin)
RN  - 4PZK9FJC4Z 
      ((4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic 
      acid)
SB  - IM
MH  - Albuminuria/drug therapy/genetics/metabolism
MH  - Analysis of Variance
MH  - Animals
MH  - Blotting, Western
MH  - Chemokine CCL2/genetics/metabolism
MH  - Diabetes Mellitus, Experimental/drug therapy/genetics/*metabolism
MH  - Diabetic Nephropathies/genetics/*metabolism/prevention & control
MH  - Fluorescent Antibody Technique
MH  - Immunoprecipitation
MH  - Kidney/drug effects/*metabolism
MH  - Male
MH  - Mice
MH  - Osteopontin/genetics/metabolism
MH  - PPAR delta/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-bcl-6/genetics/metabolism
MH  - Thiazoles/pharmacology/therapeutic use
PMC - PMC3046857
EDAT- 2011/01/29 06:00
MHDA- 2011/04/26 06:00
PMCR- 2012/03/01
CRDT- 2011/01/29 06:00
PHST- 2011/01/29 06:00 [entrez]
PHST- 2011/01/29 06:00 [pubmed]
PHST- 2011/04/26 06:00 [medline]
PHST- 2012/03/01 00:00 [pmc-release]
AID - db10-1361 [pii]
AID - 1361 [pii]
AID - 10.2337/db10-1361 [doi]
PST - ppublish
SO  - Diabetes. 2011 Mar;60(3):960-8. doi: 10.2337/db10-1361. Epub 2011 Jan 26.