title: Peroxisome proliferator-activated receptor delta protects against obesity-related glomerulopathy through the P38 MAPK pathway.
abstract: OBJECTIVE
  Obesity is a prominent component of metabolic syndrome and a major risk factor for renal disease. The aim of this study was to explore the effect of cross-talk between peroxisome proliferator-activated receptor (PPAR)δ and p38 mitogen-activated protein kinase (p38 MAPK) on obesity-related glomerulopathy.
  
  
  METHODS
  Male Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet for 32 weeks. Glomerular mesangial cells HBZY-1 and mature differentiation 3T3-L1 cells were cocultured and were transfected with PPARδ-expressing vectors or treated with agonist or inhibitor of PPARδ or p38 MAPK.
  
  
  RESULTS
  Rats on a high-fat diet showed typical characteristics of metabolic syndrome including obesity, dyslipidemia, insulin resistance, and hypertension. Rats on a high-fat diet also had significant glomerular hypertrophy and extracellular matrix accumulation, which were accompanied by increased p38 MAPK phosphorylation and decreased PPARδ expression in the kidney tissue. The roles of p38 MAPK and PPARδ in a coculture system of mesangial cells and mature differentiation 3T3-L1 cells were further explored. PPARδ suppression promoted laminin and type IV collagen secretion through p38 MAPK phosphorylation in mesangial cells, whereas PPARδ overexpression or PPARδ agonist attenuated phosphorylation of p38 MAPK and laminin and type IV collagen secretion.
  
  
  CONCLUSIONS
  The characteristics of obesity-related glomerulopathy, which might be partly caused by PPARδ suppression-induced p38 MAPK activation and laminin and type IV collagen secretion was demonstrated.
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Chongqing Hypertension Institut, Chongqing 400042, China.
authors.forename: Zhencheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Yinxing
authors.initials: Y
authors.lastname: Ni
authors.forename: Peijian
authors.initials: P
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Hongbo
authors.initials: H
authors.lastname: He
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Tingbing
authors.initials: T
authors.lastname: Cao
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Luo
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D003094:Collagen / Q000037:antagonists & inhibitors / Q000378:metabolism; D059305:Diet, High-Fat; D005920:Glomerular Mesangium / Q000166:cytology / Q000473:pathology; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology*; D007797:Laminin / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism / Q000473:pathology; D024821:Metabolic Syndrome / Q000150:complications / Q000503:physiopathology; D051379:Mice; D048308:Mitogen-Activated Protein Kinase 14 / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007797:Laminin; D047494:PPAR delta; D003094:Collagen; D048308:Mitogen-Activated Protein Kinase 14