title: Medium from mesangial cells incubated with aggregated IgA1 from IgA nephropathy patients reduces podocyte adhesion through activation of the renin angiotensin system.
abstract: BACKGROUND
  Podocyte injury plays an important role in glomerulosclerosis in IgA nephropathy (IgAN), and detachment from the glomerular basement membrane is the main cause of podocyte damage. In a previous study we found that medium from mesangial cells incubated with aggregated IgA1 (aIgA1) isolated from IgAN patients decreased podocyte adhesive capacity. However, the underlying mechanism remains unclear.
  
  
  METHODS
  Podocytes were incubated in medium from mesangial cells incubated with aIgA1 isolated from IgAN patients, enalaprilat (10-5 M) and chymostatin (20 μM), or with enalaprilat and chymostatin separately. Podocyte adhesive capacity was evaluated by cell counting and hexosaminidase assay. Expression of the renin angiotensin system was measured by real-time PCR, Western blot analysis and ELISA.
  
  
  RESULTS
  Angiotensinogen, renin and angiotensin II type 1 and 2 receptors mRNA and protein expression, angiotensin-converting enzyme activity, and angiotensin II levels increased in podocyte lysates and conditioned culture media on exposure to mesangial medium containing aIgA1 from IgAN patients (P <0.05). Enalaprilat or chymostatin partly improved the reduced adhesive capacity of podocytes compared to cells exposed to mesangial medium (P <0.05), but it was still lower than for podocytes exposed to mesangial medium containing aIgA1 from healthy controls (P <0.05).
  
  
  CONCLUSIONS
  Our findings indicate that activation of the renin angiotensin system in podocytes is partly involved in downregulation of adhesive capacity in podocytes by mesangial medium in IgA nephropathy.
authors.affiliation: Division of Nephrology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, CN, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.forename: ZengChun
authors.initials: Z
authors.lastname: Ye
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
authors.forename: Tanqi
authors.initials: T
authors.lastname: Lou
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D018929:Cell Culture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007070:Immunoglobulin A / Q000494:pharmacology*; D051379:Mice; D050199:Podocytes / Q000276:immunology / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
chemical_list: D017077:Culture Media, Conditioned; D007070:Immunoglobulin A