title: Microarray and bioinformatic detection of novel and established genes expressed in experimental anti-Thy1 nephritis.
abstract: BACKGROUND
  Microarray technology is a powerful tool that can probe the molecular pathogenesis of renal injury. In this present study microarray analysis was used to monitor serial changes in the renal transcriptome of a rat model of mesangial proliferative glomerulonephritis. Administration of anti-Thy1 antibody results in phases of acute mesangial injury (day 2), cell proliferation (day 5), matrix expansion (days 5 and 7), and subsequent healing (day 14).
  
  
  METHODS
  Using Affymetrix (RAE230A) microarrays coupled with sequential primary biologic function-focused and secondary "baited" global cluster analysis, a cohort of established and putative novel modulators of mesangial cell turnover was identified.
  
  
  RESULTS
  Cluster analysis of proliferative genes identified a number of gene expression profiles. The most striking pattern was increased gene expression at day 5, a cluster that included platelet-derived growth factor (PDGF), cyclins and transforming growth factor-beta (TGF-beta). The gene expression patterns identified by primary focused cluster analysis were used as bioinformatic bait and resulted in the identification of novel families of genes such as the S100 family. The expression of established and novel genes was confirmed using reverse transcription-polymerase chain reaction (RT-PCR). Next, in vivo gene expression was compared to PDGF-stimulated mesangial cells in vitro revealing similar patterns of dysregulation.
  
  
  CONCLUSIONS
  Transcriptomic analysis defined both known and novel molecules involved in mesangial cell proliferation in vitro and in vivo and defined a panel of molecules that are potential contributors to mesangial cell dysfunction in glomerular disease.
authors.affiliation: Department of Medicine and Therapeutics, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland. dsadlier.genome@mater.ie
authors.forename: Denise M
authors.initials: DM
authors.lastname: Sadlier
authors.forename: Xuesong
authors.initials: X
authors.lastname: Ouyang
authors.forename: Blaithin
authors.initials: B
authors.lastname: McMahon
authors.forename: Wei
authors.initials: W
authors.lastname: Mu
authors.forename: Ryuji
authors.initials: R
authors.lastname: Ohashi
authors.forename: Karen
authors.initials: K
authors.lastname: Rodgers
authors.forename: David
authors.initials: D
authors.lastname: Murray
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Catherine
authors.initials: C
authors.lastname: Godson
authors.forename: Peter
authors.initials: P
authors.lastname: Doran
authors.forename: Hugh R
authors.initials: HR
authors.lastname: Brady
authors.forename: Rick J
authors.initials: RJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D016000:Cluster Analysis; D019295:Computational Biology; D004195:Disease Models, Animal; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics*; D006801:Humans; D007518:Isoantibodies; D050527:Mesangial Cells / Q000166:cytology / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis / Q000592:standards; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007518:Isoantibodies; D010982:Platelet-Derived Growth Factor; C035678:anti-Thy antibody