title: Protective effects of PPARγ agonist in acute nephrotic syndrome.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have beneficial effects on renal structure and function in models of diabetes and chronic kidney diseases. However, the increased incidence of weight gain and edema potentially limits their usefulness. We studied an acute minimal-change disease-like nephrotic syndrome model to assess effects of PPARγ agonist on acute podocyte injury and effects on fluid homeostasis.
  
  
  METHODS
  Acute podocyte injury and nephrotic syndrome were induced by puromycin aminonucleoside (PAN) injection in rats.
  
  
  RESULTS
  PPARγ agonist, given at the time or after, but not before PAN, reduced proteinuria, restored synaptopodin, decreased desmin and trended to improve foot process effacement. There was no significant difference in glomerular filtration, effective circulating volume, blood pressure or fractional sodium excretion. PAN-injured podocytes had decreased PPARγ, less nephrin and α-actinin-4, more apoptosis and reduced phosphorylated Akt. In PAN-injured cultured podocytes, PPARγ agonist also reversed abnormalities only when given simultaneously or after injury.
  
  
  CONCLUSIONS
  These results show that PPARγ agonist has protective effects on podocytes in acute nephrotic syndrome without deleterious effects on fluid homeostasis. PPARγ agonist-induced decrease in proteinuria in acute nephrotic syndrome is dependent at least partially on regulation of peroxisome proliferator-response element-sensitive gene expression such as α-actinin-4 and nephrin and the restoration of podocyte structure.
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Zuo
authors.forename: Hai-Chun
authors.initials: HC
authors.lastname: Yang
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Potthoff
authors.forename: Behzad
authors.initials: B
authors.lastname: Najafian
authors.forename: Valentina
authors.initials: V
authors.lastname: Kon
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Ma
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Fogo
mesh_terms: D000185:Actinin / Q000378:metabolism; D000208:Acute Disease; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D051399:Aquaporin 2 / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003893:Desmin / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007124:Immunoenzyme Techniques; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D050199:Podocytes / Q000166:cytology / Q000187:drug effects*; D011507:Proteinuria / Q000517:prevention & control; D011692:Puromycin Aminonucleoside / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014882:Water-Electrolyte Balance / Q000187:drug effects*
chemical_list: D000903:Antibiotics, Antineoplastic; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D003893:Desmin; D053503:Epithelial Sodium Channels; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000185:Actinin; D011692:Puromycin Aminonucleoside; D000077205:Pioglitazone