title: Mesangial medium from IgA nephropathy patients induces podocyte epithelial-to-mesenchymal transition through activation of the phosphatidyl inositol-3-kinase/Akt signaling pathway.
abstract: BACKGROUND
  Podocyte injury plays an important role in glomerulosclerosis in IgA nephropathy (IgAN). Eepithelial-to-mesenchymal transition (EMT) caused by different factors is the main reason for podocyte damage. This study hypothesized that conditioned mesangial medium may induced EMT process of podocytes and thereby lead to glomerular injury or sclerosis.
  
  
  METHODS
  Podocytes were incubated in medium from mesangial cells incubated with aggregated IgA1(aIgA1) isolated from IgAN patients. Wortmannin were used to inhibit phosphatidylinositol-3-kinase (PI3-K) in podocytes.
  
  
  RESULTS
  Western blot analysis, real-time PCR and confocal fluorescent microscopy demonstrated that reduced expression of P-Cadherin, Zonula occludens-1 (ZO-1) and podocin, increased expression of fibroblast -specific protein (FSP-1), α-smooth muscle action(α-SMA) and desmin in podocytes exposed to medium from mesangial cells incubated with aIgA1 isolated from IgAN patients compared with podocytes cultured in RPMI 1640 medium containing 0.5% fetal bovine serum ( FBS) (p<0.05). Mesangial medium resulted in a greater albumin influx across the podocyte monolayer (p<0.05). Phosphorylation of Akt increased with this medium, as indicated by an increase in the p-Akt/Akt ratio. Treatment with wortmannin partly restored the changes in epithelial and mesenchymal markers and albumin influx. IgAN patients with massive proteinuria showed remarkable α-SMA and FSP-1 expression in podocytes.
  
  
  CONCLUSIONS
  Our findings indicated that mesangial medium from cells incubated with aIgA1 isolated from IgAN patients induced EMT in podocytes and the PI3-K/ Akt-signaling pathway was involved in the process.
authors.affiliation: Division of Nephrology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.forename: ZunFu
authors.initials: Z
authors.lastname: Ke
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.forename: Cui-Cui
authors.initials: CC
authors.lastname: Li
authors.forename: Can-Ming
authors.initials: CM
authors.lastname: Li
authors.forename: ZengChun
authors.initials: Z
authors.lastname: Ye
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Tanqi
authors.initials: T
authors.lastname: Lou
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002846:Chromatography, Affinity; D003470:Culture Media; D017931:DNA Primers; D004789:Enzyme Activation; D058750:Epithelial-Mesenchymal Transition; D019084:Fluorescent Antibody Technique, Indirect; D005920:Glomerular Mesangium / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000378:metabolism*; D006801:Humans; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D050199:Podocytes / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D003470:Culture Media; D017931:DNA Primers; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt