title: Microarray and bioinformatics analysis of gene expression in experimental membranous nephropathy.
abstract: BACKGROUND
  Passive Heymann nephritis (PHN), the best characterized animal model of experimental membranous nephropathy, is characterized by subepithelial immune deposits, podocyte foot processes effacement and massive proteinuria beginning 4 days following disease induction. Although single genes involved in PHN have been studied, no whole genome-wide expression analysis of kidney tissue has been performed.
  
  
  METHODS
  Microarray analysis was performed to identify gene expression changes in PHN rat kidneys during the onset of proteinuria.
  
  
  RESULTS
  Our results showed that 234 transcripts were differentially expressed in diseased animals compared to controls. Genes exclusively upregulated in diseased animals were mainly required for cell structure and motility, immunity and defense, cell cycle, and developmental processes. The single most increased gene was transgelin (Tagln) showing a 70-fold upregulation in animals with PHN. Protein-protein interaction analysis revealed the following four processes of major relevance in disease manifestation: (i) DNA damage and repair; (ii) changes in the extracellular matrix; (iii) deregulation of cytokines and growth factors, as well as (iv) rearrangements of the cytoskeleton.
  
  
  CONCLUSIONS
  We show for the first time the complex interplay between multiple different genes in experimental membranous nephropathy, supporting a role for genomic approaches to better understanding and defining specific disease processes.
authors.affiliation: Division of Nephrology & Hypertension, University of Washington School of Medicine, Seattle, Wash. 98195, USA. phauser@u.washington.edu
authors.forename: Peter V
authors.initials: PV
authors.lastname: Hauser
authors.forename: Paul
authors.initials: P
authors.lastname: Perco
authors.forename: Irmgard
authors.initials: I
authors.lastname: Mühlberger
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Pippin
authors.forename: Mary
authors.initials: M
authors.lastname: Blonski
authors.forename: Bernd
authors.initials: B
authors.lastname: Mayer
authors.forename: Charles E
authors.initials: CE
authors.lastname: Alpers
authors.forename: Rainer
authors.initials: R
authors.lastname: Oberbauer
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Shankland
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics*; D015433:Glomerulonephritis, Membranous / Q000235:genetics* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; C051615:transgelin