title: Differential kidney proteome profiling in a murine model of renal fibrosis under treatment with mycophenolate mofetil.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of mycophenolate mofetil (MMF) using differential kidney proteome profiling of COL4A3-deficient mice as a model of progressive renal disease.
  
  
  METHODS
  Histological evaluation of kidney sections was performed. Total protein lysate from kidneys of placebo- and MMF-treated COL4A3-deficient mice was studied for significant differences in protein abundance using 2-dimensional electrophoresis and mass spectrometry.
  
  
  RESULTS
  While tubulointerstitial fibrosis in COL4A3-deficient mice was inhibited by MMF, 19 proteins in the kidneys were regulated: 12 with lower (ATPO, TAGL2, CAH1, TPD52, VA0D1, SERPH, GNAL, PSB6, EF1D, OTUB1, NDUS8, and NAPSA) and 7 with higher (ACADM, ACY3, CK054, ACTB/G, ACTB, UBP5, and ACY1) spot intensity. Nine differentially expressed proteins showed interaction potential (ATPO, TPD52, PSB6, EF1D, OTUB1, NAPSA, ACTB, ACTG, and UBP5).
  
  
  CONCLUSIONS
  The identified proteins take part in different signaling pathways. With the highest probability, the VEGF signaling pathway (TAGL2, EF1D, and ACTB) and hypoxia (CAH1, PSB6, and ACTG) were influenced by MMF in fibrotic conditions. Moreover, MMF may modulate antifibrotic and apoptotic pathways as well as epithelial-mesenchymal transition (EMT). Different signaling pathways may be influenced by MMF therapy. These results suggest an inhibitory effect of MMF on renal EMT in COL4A3-deficient mice. Further studies are necessary to validate these findings.
authors: Department of Clinical Chemistry, University Hospital Göttingen, Germany. darinka.petrova @ med.uni-goettingen.de
authors: Darinka T
authors: DT
authors: Petrova
authors: Franziska
authors: F
authors: Brehmer
authors: Frank C
authors: FC
authors: Schultze
authors: Abdul R
authors: AR
authors: Asif
authors: Oliver
authors: O
authors: Gross
authors: Michael
authors: M
authors: Oellerich
authors: Gunnar
authors: G
authors: Brandhorst